Engineered newcastle disease virus vector and uses thereof

ABSTRACT

An engineered Newcastle Disease Virus (NDV) vector is provided. In particular, the present disclosure provides methods of treating or preventing a disease such as cancer, or an infectious disease, or methods for eliciting an immune response, with the engineered NDV vector. The engineered NDV vector provided herein is useful as an immunogenic composition, an oncolytic agent, or a vaccine.

RELATED APPLICATION

This disclosure claims benefit and priority of U.S. Provisional PatentApplication Ser. No. 63/196,489 filed Jun. 3, 2021, incorporated hereinby reference in its entirety.

INCORPORATION OF SEQUENCE LISTING

A computer readable form of the Sequence Listing“P62990US01_Sequence_Listing_ST25” (426,627 bytes), submitted viaEFS-WEB and created on Jun. 3, 2022, is herein incorporated byreference.

FIELD

The present disclosure provides engineered Newcastle Disease Virus (NDV)vectors comprising a nucleic acid having a nucleic acid sequencedescribed herein. The NDV vectors may comprise at least one heterologousnucleic acid segment encoding a therapeutic agent operably linked to aviral promoter capable of expressing the segment in a host cell. Alsoprovided are methods of treating a disease with said engineered NDVvectors and a vaccine comprising an engineered NDV vector describedherein, and methods of treating a disease with said vaccine.

BACKGROUND

Newcastle Disease Virus (NDV), also known as avian orthoavulavirus-1(AOaV-1), is an enveloped avian paramyxovirus virus with anon-segmented, negative-sense RNA genome. NDV has been studied as acandidate engineered live vaccine platform for human and veterinaryinfectious diseases. NDV may be useful as a candidate vaccine vector fora few reasons. As an avian virus, NDV is antigenically distinct fromcommon human vaccines and pathogens, averting the problem ofpre-existing immunity that would limit its efficacy in people. As anoncolytic agent, NDV has shown an excellent safety profile, wherebydirect intravenous, aerosol, or intratumoral administration of largevirus doses is well tolerated in people (Wheelock, E. F. and J. H.Dingle, 1964; Csatary, L. K., et al., 1993; Pecora, A. L, 2002). As avaccine vector in pre-clinical models, NDV-vectored vaccines have beenshown to be safe and protective in non-human primate models ofpathogenic avian influenza, Ebola, and SARS-CoV-1 (severe acuterespiratory syndrome coronavirus-1) (Bukreyev, A., et al., 2005;DiNapoli, J. M., et al., 2010; DiNapoli, J. M., et al., 2007).Additionally, the NDV viral genome is highly versatile, allowing forstable insertion and high-level expression of foreign genes such asviral antigens. Lastly, NDV is an acute cytoplasmic virus and itsgenomic RNA is tightly encapsidated by nucleocapsid protein; allfeatures that markedly mitigate concerns about insertional mutagenesisor recombination.

The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2)emerged in late 2019 as the causative agent of a severe respiratorydisease named coronavirus disease 2019 (COVID-19). The virus has beenclassified in the Coronaviridae family, β-coronavirus genus, andSarbecovirus subgenus (i.e., β-coronavirus subgroup B). Phylogeneticanalysis has shown that this virus shares ≈50% genetic similarity withMERS (Middle East Respiratory Syndrome)-CoV, ≈with SARS-CoV-1, and >90%similarity with bat β-coronaviruses. SARS-CoV-2 is transmitted throughcontact and respiratory route. In people with severe disease, morbidityand mortality are mediated by severe respiratory distress syndrome andvascular disease. The former is caused by diffuse alveolar damageassociated with virus replication in type I and II alveolar pneumocytes.Molecular effectors of tissue damage include unchecked production ofpro-inflammatory cytokines (i.e., cytokine storm), decreasedangiotensin-converting enzyme-2 (ACE2) activity, and activation of athrombo-inflammatory cascade leading to a hypercoagulable state.

Multiple research groups have been working towards production of severalvaccine platforms against SARS-CoV-2, including engineered viralvectors, nucleic acids (DNA, mRNA and self-replicating RNA), proteinsubunits, virus-like particles, and live-attenuated or inactivatedSARS-CoV-2 virions. The vast majority of these vaccines target theSARS-CoV-2 Spike (S) protein, the main neutralizing antigen against thevirus. In December 2020, two mRNA based COVID-19 vaccines(Pfizer-BioNTech and Moderna) received emergency use authorization bythe U.S. Food and Drug Administration; however, it is unclear whetherthese vaccines will have reduced efficacy against Variants of Concern(VoC), such as the South African B.1.351 variant, highlighting the needfor vaccines that induce sterilizing immunity (Peiris, M. and G. M.Leung, 2020).

Due to the relative advantages and disadvantages of different vaccinetypes, there is an ongoing need to develop and test novel vaccineplatforms and strategies. New vaccines may be critical for potentialfuture pandemics and emerging and re-emerging infections, which willrequire swift development of vaccine candidates. Live viral vectors maybe useful due to their generally high immunogenicity, ability to induceboth humoral and cellular immune responses, and the lack of a need foradjuvants.

SUMMARY

The present inventors produced an engineered (fully synthetic) NewcastleDisease Virus (NDV) vector, which is immune stimulatory and useful as atherapeutic agent for oncolytic viral therapy, or as a vaccine platformfor immunoprophylaxis. In particular, the inventors created anintra-nasally delivered, non-virulent NDV vaccine expressing theSARS-CoV-2 spike protein for protecting subjects from COVID-19 orrelated coronaviruses. The use of a non-virulent NDV strain (i.e.,lentogenic pathotype) makes the vaccine safe in both mammals and avianspecies, including poultry, which are the natural target of NDV.Intra-nasal delivery stimulates both a mucosal and systemic immuneresponse in the host, and a needle-free administration is logisticallysimpler and can ameliorate concerns associated with vaccine hesitancy.The engineered NDV vector of this disclosure can infect host cells toexpress an immunogenic agent, for example, the SARS-CoV-2 spike protein(NDV-FLS), which leads to the production of spike protein-specific serumIgG and mucosal IgA antibodies as well as spike protein-specific T cellsresponses in subjects administered the vaccine intranasally.

Accordingly, the present disclosure provides an engineered NewcastleDisease Virus (NDV) vector comprising a nucleic acid having a nucleicacid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%,99%, 99.5%, 99.9% or 100% identical to the nucleic acid sequence of anyone of SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42, wherein the nucleicacid comprises or further comprises at least one heterologous nucleicacid segment encoding a therapeutic agent operably linked to a promotercapable of expressing the segment in a host cell, wherein the nucleicacid comprises a nucleic acid sequence encoding an L protein having astabilizing segment, and wherein the nucleic acid comprises XbaI andMluI restriction endonuclease sites between nucleic acid sequencesencoding phosphoprotein and matrix protein.

The present disclosure also provides a method of treating or preventinga disease in a subject, comprising administering an engineered NDVvector comprising a nucleic acid having a nucleic acid sequence that isat least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or100% identical to the nucleic acid sequence of any one of SEQ ID NO:1-5, 9, 10, 18, 19, 23, 27, or 42, wherein the nucleic acid comprises orfurther comprises at least one heterologous nucleic acid segmentencoding a therapeutic agent operably linked to a promoter capable ofexpressing the segment in a host cell, wherein the nucleic acidcomprises a nucleic acid sequence encoding an L protein having astabilizing segment, and wherein the nucleic acid comprises XbaI andMluI restriction endonuclease sites between nucleic acid sequenceencoding phosphoprotein and matrix protein.

Also provided is use of an engineered NDV vector for treating orpreventing a disease in a subject, wherein the engineered NDV vectorcomprises a nucleic acid having a nucleic acid sequence that is at least75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or 100%identical to the nucleic acid sequence of any one of SEQ ID NO: 1-5, 9,10, 18, 19, 23, 27, or 42, wherein the the nucleic acid comprises orfurther comprises at least one heterologous nucleic acid segmentencoding a therapeutic agent operably linked to a promoter capable ofexpressing the segment in a host cell, wherein the nucleic acidcomprises a nucleic acid sequence encoding an L protein having astabilizing segment, and wherein the nucleic acid comprises XbaI andMluI restriction endonuclease sites between nucleic acid sequenceencoding phosphoprotein and matrix protein.

Further provided is use of an engineered NDV vector in the manufactureof a medicament for treating or preventing a disease in a subject,wherein the engineered NDV vector comprises a nucleic acid having anucleic acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%,97%, 98%, 99%, 99.5%, 99.9% or 100% identical to the nucleic acidsequence of any one of SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42,wherein the nucleic acid comprises a nucleic acid sequence encoding an Lprotein having a stabilizing segment, wherein the nucleic acid comprisesor further comprises at least one heterologous nucleic acid segmentencoding a therapeutic agent operably linked to a promoter capable ofexpressing the segment in a host cell, and wherein the nucleic acidcomprises XbaI and MluI restriction endonuclease sites between nucleicacid sequence encoding phosphoprotein and matrix protein.

Even further provided is an engineered NDV vector for use in treating orpreventing a disease in a subject, wherein the engineered NDV vectorcomprises a nucleic acid having a nucleic acid sequence that is at least75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or 100%identical to the nucleic acid sequence of any one of SEQ ID NO: 1-5, 9,10, 18, 19, 23, 27, or 42, wherein the nucleic acid comprises a nucleicacid sequence encoding an L protein having a stabilizing segment,wherein the nucleic acid comprises or further comprises at least oneheterologous nucleic acid segment encoding a therapeutic agent operablylinked to a promoter capable of expressing the segment in a host cell,and wherein the nucleic acid comprises XbaI and MluI restrictionendonuclease sites between nucleic acid sequence encoding phosphoproteinand matrix protein.

In an embodiment, the engineered NDV vector comprises a nucleic acidhaving a nucleic acid sequence that is at least 75%, 80%, 85%, 90%, 95%,96%, 97%, 98%, 99%, 99.5%, 99.9% A or 100% identical to the nucleic acidsequence of SEQ ID NO: 9, 10, 23, or 27. In an embodiment, theengineered NDV vector comprises a nucleic acid having a nucleic acidsequence that is at least 95% identical to the nucleic acid sequence anyone of SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42. In an embodiment,the engineered NDV vector comprises a nucleic acid having a nucleic acidsequence that is at least 99% identical to the nucleic acid sequence anyone of SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42. In an embodiment,the engineered NDV vector comprises a nucleic acid sequence consistingof the nucleic acid sequence any one of SEQ ID NO: 1-5, 9, 10, 18, 19,23, 27, or 42.

In an embodiment, the engineered NDV vector comprises a nucleic acidhaving a nucleic acid sequence a chimeric F protein, and a chimeric HNprotein, wherein the chimeric F protein comprises avian paramyxovirus 5(APMV5) F protein segment thereof at the N-terminus and an NDV F proteinsegment at the C-terminus, and wherein the chimeric HN protein comprisesan NDV HN protein segment at the N-terminus and an AMPV5 HN proteinsegment at the C-terminus. In an embodiment, the stabilizing segmentcomprises an amino acid sequence as set forth in SEQ ID NO: 20. In anembodiment, the stabilizing segment is encoded by a nucleic acidcomprising a nucleic acid sequence as set forth in SEQ ID NO: 35. In anembodiment, the chimeric F protein comprises at the C-terminus 53 aminoacid of NDV F protein from amino acid positions 501 to 553 of SEQ ID NO:28. In an embodiment, the chimeric HN protein comprises at theN-terminus 53 amino acids of NDV HN protein from amino acid positions 1to 53 of SEQ ID NO: 34. In an embodiment, the engineered NDV vector ofany one of claims 8 to 11, wherein the L protein comprises an amino acidsequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%,99.9%, or 100% identity to the amino acid sequence as set forth in SEQID NO: 11. In an embodiment, the chimeric F protein comprises an aminoacid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%,99.9%, or 100% identity to the amino acid sequence of SEQ ID NO: 12. Inan embodiment, the chimeric HN protein comprises an amino acid sequencehaving at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100%identity to the amino acid sequence of SEQ ID NO: 13.

In an embodiment, the NDV vector is lentogenic, and wherein the nucleicacid comprises a nucleic acid sequence of SEQ ID NO: 25.

Also provided is an engineered Newcastle Disease Virus (NDV) vectorcomprising a nucleic acid having a nucleic acid sequence encoding an Lprotein having a stabilizing segment, a chimeric F protein, and achimeric HN protein, wherein the chimeric F protein comprises avianparamyxovirus 5 (APMV5) F protein segment thereof at the N-terminus andan NDV F protein segment at the C-terminus, and wherein the chimeric HNprotein comprises an NDV HN protein segment at the N-terminus and anAMPV5 HN protein segment at the C-terminus. In an embodiment, thenucleic acid comprises XbaI and MluI restriction endonuclease sitesbetween nucleic acid sequence encoding phosphoprotein and matrixprotein. In an embodiment, the stabilizing segment comprises an aminoacid sequence as set forth in SEQ ID NO: 20. In an embodiment, thestabilizing segment is encoded by a nucleic acid comprising a nucleicacid sequence as set forth in SEQ ID NO: 35. In an embodiment, thechimeric F protein comprises at the C-terminus 53 amino acid of NDV Fprotein from amino acid positions 501 to 553 of SEQ ID NO: 28. In anembodiment, the chimeric HN protein comprises at the N-terminus 53 aminoacids of NDV HN protein from amino acid positions 1 to 53 of SEQ ID NO:34. In an embodiment, the L protein comprises an amino acid sequencehaving at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100%identity to the amino acid sequence as set forth in SEQ ID NO: 11. In anembodiment, the chimeric F protein comprises an amino acid sequencehaving at least 85% identity to the amino acid sequence of SEQ ID NO:12. In an embodiment, the chimeric HN protein comprises an amino acidsequence having at least 85% identity to the amino acid sequence of SEQID NO: 13. In an embodiment, the NDV vector is lentogenic, and whereinthe nucleic acid comprises a nucleic acid sequence of SEQ ID NO: 25. Inan embodiment, the nucleic acid further comprises at least oneheterologous nucleic acid segment encoding a therapeutic agent operablylinked to a promoter capable of expressing the segment in a host cell.

In another embodiment, the host cell is selected from the groupconsisting of a human, primate, murine, feline, canine, ovine, bovine,porcine, caprine, equine, lupine, vulpine, mustelid host cell and. In afurther embodiment, the promoter is capable of expressing the at leastone heterologous nucleic acid segment encoding the therapeutic agent inmuscle, airways, or lung cells.

In an embodiment, the disease is an infectious disease. In anembodiment, the infectious disease is selected from the group consistingof viral diseases such as viral hemorrhagic fevers, Ebola, Marburg virusdisease, gastroenteritis, dengue fever, West Nile fever, yellow fever,influenza, respiratory syncytial virus disease, Lassa fever, rabies,smallpox, cowpox, horsepox, monkeypox, Hantavirus pulmonary syndrome,Hendra virus disease, Nipah virus disease, human immunodeficiency virusinfection and acquired immunodeficiency disease syndrome, Hepatitis,Zika fever, Severe Acute Respiratory Syndrome (SARS), Middle EastRespiratory Syndrome (MERS), Coronavirus disease 2019 (COVID-19),infectious bronchitis, infectious laryngotracheitis, Rift Valley fever,porcine epidemic diarrhea, porcine transmissible gastroenteritis, swineacute diarrhea syndrome, feline infectious peritonitis, African swinefever, classical swine fever, and bacterial diseases including drugresistant bacterial diseases such as tuberculosis andmethicillin-resistant Staphylococcus aureus infection, and drugresistant parasitic diseases such as malaria. In an embodiment, theinfectious disease is COVID-19.

In an embodiment, the therapeutic agent comprises a SARS-CoV-2 spikeprotein. In an embodiment, the SARS-CoV-2 spike protein comprises anamino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%,99.5%, 99.9%, or 100% identity to the amino acid sequence of SEQ ID NO:6, 7, 29, 30, 31, or 41.

In an embodiment, the subject is an animal. In an embodiment, the animalis human or a veterinary animal. In an embodiment, the subject is human.In an embodiment, the subject is a veterinary animal. In an embodiment,the veterinary animal is a primate, a murine, a feline, a canine, anovine, a bovine, a porcine, a caprine, an equine, a lupine, a vulpine,or a mustelid. In an embodiment, the subject is a mustelid.

In another embodiment, the engineered NDV vector is administered orco-administered intravenously, intranasally, intratracheally,intramuscularly, or via aerosol. In an embodiment, the viral vector isdelivered to lung cells or tissues. In an embodiment, the viral vectoris delivered intranasally or intramuscularly. In an embodiment, theviral vector is delivered to an animal. In an embodiment, the viralvector is delivered to a human or a veterinary animal. In an embodiment,the veterinary animal is a primate, a murine, a feline, a canine, anovine, a bovine, a porcine, a caprine, an equine, a lupine, a vulpine,or a mustelid. In an embodiment, the viral vector is delivered to ahuman. In an embodiment, the viral vector is delivered to a mustelid.

The present disclosure also provides an isolated nucleic acid having anucleic acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%,97%, 98%, 99%, 99.5%, 99.9% or 100% identical to the nucleic acidsequence of any one of SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42,wherein the nucleic acid comprises XbaI and MluI restrictionendonuclease sites between nucleic acid sequence encoding phosphoproteinand matrix protein. In an embodiment, the nucleic acid sequence is atleast 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or 100%identical to the nucleic acid sequence of SEQ ID NO: 9, 10, 23, or 27,wherein the nucleic acid comprises XbaI and MluI restrictionendonuclease sites between nucleic acid sequence encoding phosphoproteinand matrix protein. In an embodiment, the nucleic acid comprises orfurther comprises at least one heterologous nucleic acid segmentencoding a therapeutic agent operably linked to a promoter capable ofexpressing the segment in a host cell.

In an embodiment, the nucleic acid further comprises at least oneheterologous nucleic acid segment encoding a therapeutic agent operablylinked to a promoter capable of expressing the segment in a host cell.

Further provided is a pharmaceutical composition comprising anengineered NDV vector described herein, and a pharmaceuticallyacceptable carrier. In an embodiment, the pharmaceutical composition islyophilized.

Further provided is a method of producing a protein in vivo in asubject, comprising delivering or introducing into the subject anengineered NDV vector comprising a nucleic acid having a nucleic acidsequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%,99.5%, 99.9% A or 100% identical to the nucleic acid sequence of any oneof SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42, wherein the nucleicacid comprises a nucleic acid sequence encoding an L protein having astabilizing segment, wherein the nucleic acid comprises or furthercomprises at least one heterologous nucleic acid segment encoding aprotein operably linked to a promoter capable of expressing the segmentin a host cell, and wherein the nucleic acid comprises XbaI and MluIrestriction endonuclease sites between nucleic acid sequence encodingphosphoprotein and matrix protein.

Further provided is an immunogenic composition, an oncolytic agent, or avaccine comprising an engineered NDV vector described herein fortreating a disease described herein.

Further provided is a method of eliciting an immune response, comprisingadministering to a subject an engineered NDV vector described herein,for treating a disease described herein.

Further provided is a method of treating cancer, comprisingadministering to a subject an engineered NDV vector described herein,wherein the NDV vector comprises a nucleic acid having a nucleic acidsequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%,99.5%, 99.9% or 100% identical to the nucleic acid sequence of any oneof SEQ ID NO: 1, 5, 9, 10, 23, or 27.

Further provided is a method for selecting an engineered NDV vectorgenome comprising a stabilizing segment in L gene, the method comprises:

-   -   a) growing bacterial cells comprising an engineered NDV vector        genome in a growth medium broth;    -   b) growing the bacterial cells on an agar-growth medium, wherein        the agar-growth medium comprises a selection agent;    -   c) identifying small bacterial cells colonies having about 0.5        mm to about 1 mm in diameter after at least 24 hours of growth;    -   d) repeating step a) to step c) two to nine times to enrich for        small bacterial cell colonies; and    -   e) isolating the engineered NDV vector genome from the small        bacterial cells colonies,    -   wherein the small bacterial cells colonies comprise stable        engineered NDV vector genome having the stabilizing segment in L        gene.

Other features and advantages of the present disclosure will becomeapparent from the following detailed description. It should beunderstood, however, that the detailed description and the specificExamples while indicating preferred embodiments of the disclosure aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the disclosure will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments are described below in relation to the drawings in which:

FIG. 1A shows a schematic representation of an engineered NDV vectorwith XbaI and MluI restriction endonuclease sites introduced between theP and M genes. GFP, full-length spike protein (FLS) or the C-terminaltruncated spike (Δ19S) genes were inserted into this site.

FIG. 1B shows virus replication and cytopathic effect in cells. DF-1cells were infected with NDV-FLS, NDV-Δ19S, or NDV-GFP virus at amultiplicity of infection (MOI) of 10. The first row showsimmunofluorescence staining for NDV ribonucleoprotein. The second rowshows bright field. Both NDV-FLS and NDV-Δ19S replicated in cells,showing accumulation of NDV nucleoprotein, and caused cytopathic effect(syncytia), similar to the NDV-GFP control.

FIG. 1C shows results of agarose gel electrophoresis of PCR amplifiedproducts from DF-1 cells infected with engineered NDV expressingSARS-CoV-2 spike protein to confirm spike protein expression. DF-1 cellswere infected with either NDV-FLS, NDV-Δ19S, or NDV-GFP. RNA wasextracted from cells 12 hours later and reverse transcribed to cDNA withM-MuLV-RT. Primers were used to target both the FLS and the 119S (lanes1-6); or only the full-length spike (lanes 7-12). Lanes 1 and 7:NDV-FLS; lanes 2 and 8: NDV-Δ19S; Lanes 3 and 9: NDV-GFP; Lanes 4 and10: plasmid clone of NDV-full-length spike protein (positive control);Lanes 5 and 11: uninfected DF1 cells (negative control); Lanes 6 and 12:no-template control. M=GeneRuler 50 bp DNA Ladder (Thermo FisherScientific).

FIG. 1D shows Western blots of whole cell lysates from DF-1 cellsinfected with an MOI of 5, with either (1) NDV-FLS; (2) NDV-Δ19S; (3)NDV-GFP; or (4) uninfected negative control to confirm spike proteinexpression. Immunoblotting was done with rabbit-anti-spike protein(NB100-56578; Novus Biologicals), mouse-anti-NDV (NBP2-11633; NovusBiologicals), and mouse-anti-actin (MA5-15739; ThermoFisher). A strongband at around 180 kDa corresponding to the spike protein is detected inthe lysate of cells infected with NDV-FLS and -SΔ19, but not in cellsinfected with NDV-GFP or uninfected cells (control). Infection wasconfirmed by the presence of bands corresponding to theribonucleoprotein for NDV in infected cells.

FIG. 1E shows Western blots of purified viruses. 1.0×10⁷ focus formingunits (FFU) of (1) NDV-FLS; (2) NDV-Δ19S; or (3) NDV-GFP vectors wereused for Western blotting using a primary rabbit anti-spike proteinantibody (top), or a primary mouse anti-NDV ribonucleoprotein antibody(bottom), with the same antibodies described for FIG. 1D. The blot showsincorporation of the spike protein into the purified virions, whileNDV-Δ19S and NDV-GFP control shows no transgene expression.

FIG. 1F shows crystal violet staining of DF-1 cells infected withNDV-GFP, NDV-FLS, or NDV-Δ19S vector. DF-1 cells in 6-well plates wereinfected with each of NDV-GFP, NDV-FLS, or NDV-Δ19S virus at an MOI of0.1. Cells were grown in DMEM with 2% FBS supplemented with 5% allantoicfluid. 24 hours post-infection (hpi), media was removed, cells werewashed in PBS, fixed with methanol/acetone for 20 minutes at −20° C.,and stained with crystal violet.

FIG. 1G shows fusogenicity score of NDV-GFP, NDV-FLS, and NDV-Δ19S.Fusogenicity score was calculated by dividing the number of nuclei bythe number of cells in four fields of view per each of the threebiological replicates. Counting was assisted using ImageJ (U.S. NationalInstitutes of Health, Bethesda, Md., USA). The score for each virus wasnormalized to the non-infected negative control, and averages werecompared using an ANOVA and a Kruskal-Wallis multiple comparisons test.NDV-FLS showed less fusogenicity compared to the other viruses(***p<0.001).

FIG. 2 shows an immunoblot from cell lysates infected with NDV-FLS,NDV-Δ19S, and NDV-GFP, as well as the purified viruses. The blot showsefficient incorporation of spike protein into the NDV virion (first laneof top and middle blots, after molecular weight marker [MW]).Additionally, overexposure of a Western blot for spike protein revealsthe presence of C-terminal truncated spike protein in the NDV-Δ19Svirion (middle blot, rectangular box), albeit at much lower intensitythan the full-length spike protein in the NDV-FLS virion. This showsthat specific cytoplasmic transport signals are needed to enableefficient incorporation of the transgene on the NDV virion's surface.

FIG. 3 shows that neutralizing antibodies directed against SARS-CoV-2spike protein do not block NDV-FLS or NDV-Δ19S infection ofHEK293T-hACE2 cells. 1000 focus-forming units (FFU) of NDV-FLS, NDV-Δ19Sor NDV-GFP were incubated with an antibody against the SARS-CoV-2 spikeprotein receptor binding domain (MA5-35958) at multiple dilutions (10ug/mL, 5 ug/mL, 2.5 ug/mL down to 0.31 ug/mL [1/25]) for 1 h at roomtemperature with rocking plus 30 min at 37° C. HEK293T-hACE2 cells (2%FBS, DMEM, 5% allantoic fluid) were infected with the virus-Ab mixtureand immunofluorescence assay was performed three days post infection.Images for the first three antibody dilutions are shown. These resultsshow that neutralizing antibodies against SARS-CoV-2 spike protein donot affect NDV-FLS or NDV-Δ19S infection. When cells were incubated withhyperimmune serum from chickens vaccinated against NDV, the NDV-FLS wasfully neutralized, suggesting that additional S protein on the surfacedoes not functionally allow the virus to enter the cells.

FIG. 4 shows lyophilized NDV-FLS virus retains infectivity. Triplicatesamples of NDV-FLS were either left untreated or adjusted to a finalconcentration of 5% sucrose, 5% sucrose/5% Iodixanol or mixed 1:1 with astabilizing agent comprised of 10% lactose, 2% peptone, 10 mM Tris-HCl,pH 7.6 and lyophilized at 44×10⁻³ MBAR and −52° C. for 16 hr.Lyophilized samples were stored at 4° C. for 48 hours before beingresuspended in 1 mL 5% sucrose/PBS and titered by TCID50 on DF-1 cells.Statistical analysis was completed by using a two-way analysis ofvariance with Tukey's multiple comparisons test with significance set atp<0.05.

FIG. 5 shows quantification of spike protein-specific CD8+ T cellresponses. Groups of male Balb/c mice were administered with 5×10⁵,1×10⁶ or 1×10⁶ PFU of NDV-FLS in either sucrose of iodixanolintranasally. After 32 days, mice were boosted with the same dose ofvaccine via the same route (intranasal). Five days after boost, the micewere euthanized and spike protein-specific CD8 T cell responses werequantified in the blood, spleen, bronchoalveolar fluid (BALF), and lung.

FIG. 6 shows quantification of spike protein-specific CD4+ T cellresponses. Groups of male Balb/c mice were administered with 5×10⁵,1×10⁶ or 1×10⁶ PFU of NDV-FLS in either sucrose of iodixanolintranasally. After 32 days, mice were boosted with the same dose ofvaccine via the same route (intranasal). After 32 days, mice wereboosted with the same dose of vaccine via the same route ofadministration. Five days after boost, the mice were euthanized andspike protein-specific CD8 T cell responses were quantified in theblood, spleen, bronchoalveolar fluid (BALF), and lung.

FIG. 7 shows the kinetics of spike protein-specific CD8+ and CD4+ Tcells in the blood of vaccinated mice. Male C57BL/6 or Balb/c mice werevaccinated using either intranasal or intramuscular delivery of 5×10⁶FFU NDV-FLS, with a boost delivered through the same route and same dose32 days post prime. At day 10 post-vaccine administration, a subset(n=4) of mice were terminally bled and the spike protein specific CD8+and CD4+ T cell responses quantified. Mice were non-terminally bledprior to being boosted on day 28, and then bled again on days 5 and 10post-boost. Spike protein specific CD8+ and CD4+ T cell responses werequantified in the collected blood.

FIG. 8 shows killing of murine acute myeloid leukemia (AML) C1498 cellsin vitro by mesogenic NDV-GFP-GM (i.e., the mesogenic version of the NDVbackbone expressing the GFP protein). C1498 cells were infected atdifferent MOIs, spanning 0.0001 to 100, and after 72 days, the metabolicactivity of infected cells was evaluated by Resazurin assay as anindication of the cytolytic potential of the tested viruses. Testedviruses include the mesogenic NDV-GFP-GM (Guelph mesogenic), thelentogenic NDV-GFP-GL, and a hyper-fusogenic mesogenic NDV-GFP-NY.Results show that NDV-GFP-GM caused a significantly higher drop inmetabolic activity compared to the other two tested viruses (*p<0.05,**p<0.01, ****p<0.0001).

FIG. 9A shows the percentage of NK cells expressing the early activationmarker CD69, in the blood of ID8 ovarian tumor bearing mice 36 hoursafter intravenous injection of 1×10⁸ PFU NDV-F3aa-GFP (mesogenic). NDV:Newcastle disease virus; PBS: phosphate-buffered saline mock controlgroup; * p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; ns=not significant.

FIG. 9B shows a graph depicting the percentage of NK cells in the bloodof ID8 ovarian tumor bearing mice that are IFNy+, 36 hours postintravenous injection of 1×10⁸ PFU NDV-F3aa-GFP (mesogenic). NDV:Newcastle disease virus; PBS: phosphate-buffered saline mock controlgroup; *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; ns=not significant.

FIG. 10 shows an immunoblot of prefusion stabilized SARS-CoV-2 spike(PFS) in the allantoic fluid of embryonated eggs inoculated withNDV-PFS. A 6% SDS-PAGE gel and rabbit anti-SARS-CoV-2 S1 (dilution:1:1000; PA5-81795; ThermoFisher) was used for detection of SARS-CoV-2spike (black arrow). A 10% SDS-PAGE gel and mouse anti-NDVribonucleoprotein (dilution: 1:5000; NBP2-11633; Novus Biologicals) wasused for detection of NDV. 20 μL of allantoic fluid was loaded in forsamples. NDV-GFP was loaded as a control. MW used was the PageRuler™Plus Prestained Protein Ladder (Thermo Scientific).

FIG. 11 shows graphs of results on protection from weight loss inNDV-COVID-19 vaccinated hamsters challenged with SARS-CoV-2. Groups ofeight Syrian Golden hamsters were anaesthetized with inhalationisoflurane and administered 1E7 PFU/animal of recombinant NDV-GFP,NDV-FLS, or NDV-PFS via the intranasal (IN) route. For the prime/boostgroups, 28 days following the initial vaccine administration, hamsterswere administered a second dose of the homologous vaccine (1E7PFU/animal by IN route). At 28 days post-prime or 28 dayspost-prime/boost, hamsters were moved into a CL-3 facility,anaesthetized with inhaled isoflurane and infected SARS-CoV-2. Challengedose: Alpha variant @ 8.5E4 PFU/animal by IN, Ancestral (Wuhan) @ 1E5PFU/animal by IN. After recovery from anesthetic hamsters were monitoreddaily throughout the course of infection. Body weights of hamsters wererecorded daily. Error bars represent mean+/−SEM.

FIG. 12 shows graphs depicting SARS-CoV-2 viral RNA copies in the lungand nasal turbinates of vaccinated and challenged Syrian hamsters. At 5days post challenge with Alpha variant @ 8.5E4 PFU/animal by IN orAncestral (Wuhan) @ 1E5 PFU/animal by IN, vaccinated hamsters wereeuthanized and viral RNA copies in the lung and nasal turbinatesquantified by qRT-PCR. A standard curve produced with synthesized targetDNA was run with every plate and used for the interpolation of viralgenome copy numbers. Viral RNA levels are reported as genome copynumber. Error bars represent mean+/−SEM. Differences in the magnitude ofvirus copy number were assessed by Kruskall-Wallis test with Dunn's testfor multiple comparisons.

FIG. 13 shows graphs depicting infectious SARS-CoV-2 in the lung andnasal turbinates of vaccinated and challenged Syrian hamsters. At 5 dayspost challenge with Alpha variant @ 8.5E4 PFU/animal by IN or Ancestral(Wuhan) @ 1E5 PFU/animal by IN, vaccinated hamsters were euthanized andinfectious titers of SARS-CoV-2 in the lung and nasal turbinatesdetermined. Homogenized tissue samples were serially diluted 10-fold inmedia and dilutions were then added to 96-well plates of 95% confluentVero cells containing 504 of the media in replicates of three andincubated for five days at 37° C. with 5% CO₂. Plates were scored forthe presence of cytopathic effect on day five after infection. Titerswere calculated using the Reed-Muench method, converted to PFU aftermultiplying by 0.69 and reported as PFU/g of tissue.

DETAILED DESCRIPTION

Unless otherwise indicated, the definitions and embodiments described inthis and other sections are intended to be applicable to all embodimentsand aspects of the present disclosure herein described for which theyare suitable as would be understood by a person skilled in the art.

In understanding the scope of the present disclosure, the term“comprising” and its derivatives, as used herein, are intended to beopen ended terms that specify the presence of the stated features,elements, components, groups, integers, and/or steps, but do not excludethe presence of other unstated features, elements, components, groups,integers and/or steps. The foregoing also applies to words havingsimilar meanings such as the terms, “including”, “having” and theirderivatives. The term “consisting” and its derivatives, as used herein,are intended to be closed terms that specify the presence of the statedfeatures, elements, components, groups, integers, and/or steps, butexclude the presence of other unstated features, elements, components,groups, integers and/or steps. The term “consisting essentially of”, asused herein, is intended to specify the presence of the stated features,elements, components, groups, integers, and/or steps as well as thosethat do not materially affect the basic and novel characteristic(s) offeatures, elements, components, groups, integers, and/or steps.

As used herein, the singular forms “a”, “an” and “the” include pluralreferences unless the content clearly dictates otherwise.

Compositions

The term “Newcastle Disease Virus” (NDV), as used herein, includeswithout limitation, avian orthoavulavirus-1 (AOaV-1) and variantsthereof. The genome of NDV is single-stranded, negative-sense,non-segmented RNA comprising six genes in the order 3′-NP-P-M-F-HN-L-S′encoding six structural proteins: nucleocapsid protein (NP),phosphoprotein (P), matrix protein (M), fusion protein (F),haemagglutinin-neuraminidase (HN), and a large polymerase protein (L).The NDV vector genome is packaged within an envelope (membrane), whichis made of lipid bilayer, HN protein, and F protein. The M protein formsa grid-like array on the inner surface of the viral envelope. Inside theenvelope the NP protein is tightly bound to the vector genome, forming anucleocapsid complex. The L protein and P protein are loosely bound tonucleocapsid complex. NDV strains can be pathotypically categorized intothree groups: velogenic (i.e. highly virulent), mesogenic (i.e.intermediate virulence), and lentogenic (i.e. non-virulent). Velogenicstrains produce severe nervous and respiratory signs, spread rapidly,and have high mortality rate in birds. Mesogenic strains cause coughing,affect egg quality and production, and have low mortality rate in birds.Lentogenic strains produce mild signs with negligible mortality inbirds. Although NDV can infect humans, most cases are non-symptomatic,and only very rarely it causes a mild fever and/or conjunctivitis. Anucleic acid sequence that defines a strain as lentogenic isGGGAGACAGGGGCGCC (SEQ ID NO: 25), which is translated to GRQGRL (SEQ IDNO: 26) found in the F protein encoded by a nucleic acid sequence inGenbank accession number AF077761.1. A strain is mesogenic when there isa 3 amino acid change in the F gene, i.e. from GRQGRL to RRQRRF at aminoacid positions 112, 115, and 117 in reference SEQ ID NO: 28. In someembodiments of this disclosure, the NDV vector is lentogenic. In someembodiments, the NDV vector comprises a nucleic acid comprising anucleic acid sequence of SEQ ID NO: 25 or encodes the amino acidsequence of SEQ ID NO: 26. In some embodiments, the NDV vector ismesogenic. In some embodiments, the NDV vector comprises a nucleic acidcomprising a nucleic acid sequence of SEQ ID NO: 23 or 27, or encodesthe amino acid sequence RRQRRF (SEQ ID NO: 36).

As used herein, “transduction” of a cell by a viral vector means entryof the viral vector into the cell and transfer of genetic material intothe cell by which nucleic acid incorporated in the viral vector istransferred into the cell.

The term “nucleic acid”, “nucleic acid molecule” or its derivatives, asused herein, is intended to include unmodified DNA or RNA or modifiedDNA or RNA. For example, the nucleic acid molecules of the disclosurecan be composed of single- and double-stranded DNA, DNA that is amixture of single- and double-stranded regions, single- anddouble-stranded RNA, and RNA that is a mixture of single- anddouble-stranded regions, hybrid molecules comprising DNA and RNA thatmay be single-stranded or, more typically double-stranded or a mixtureof single- and double-stranded regions. In addition, the nucleic acidmolecules can be composed of triple-stranded regions comprising RNA orDNA or both RNA and DNA. The nucleic acid molecules of the disclosuremay also contain one or more modified bases or DNA or RNA backbonesmodified for stability or for other reasons. “Modified” bases include,for example, tritiated bases and unusual bases such as inosine. Avariety of modifications can be made to DNA and RNA; thus “nucleic acidmolecule” embraces chemically, enzymatically, or metabolically modifiedforms. The term “polynucleotide” shall have a corresponding meaning.

As used herein, the term “polypeptide” encompasses both peptides andproteins, and fragments thereof of peptides and proteins, unlessindicated otherwise. In one embodiment, the therapeutic agent is apolypeptide.

As used herein, the term “vector”, “viral vector”, “viral particle”, or“delivery vector”, and their derivatives, refer to a particle thatfunctions as a nucleic acid delivery vehicle, and which comprises theviral nucleic acid (i.e., the viral vector genome) packaged within theparticle. Viral vectors according to the present disclosure package aNDV vector genome. A “heterologous nucleic acid” or “heterologousnucleotide sequence” is a sequence that is not naturally occurring inthe virus, i.e. a transgene. In general, the heterologous nucleic acidor nucleotide sequence comprises an open reading frame that encodes apolypeptide and/or a non-translated RNA.

The term “engineered Newcastle Disease Virus vector” or “engineered NDVvector” comprises an engineered (also interchangeably referred as“recombinant”) NDV vector genome packaged within an envelope, i.e. a DNAcopy of the NDV antigenome comprised in an expression plasmid. Theengineered NDV vector genome is capable of generating mRNA much like anative negative-sense NDV genome is capable of generating mRNA. Theengineered NDV vector genome has a promoter, for example, an RNApromoter such as T7 immediately upstream of the 5′ end of theantigenome, or any suitable promoter known in the art, which drivesexpression of the virus RNA genome. The expression of a heterologousnucleic acid (transgene) such as one that encodes an immunogenic agentis driven by a typical NDV genome promoter. The T7 promoter, followed by3 non-template guanines, is placed immediately upstream of the firstnucleotide of the NDV vector genome. The engineered NDV vector genomedescribed herein contains unique restriction sites for endonucleasessuch as XbaI and MluI for use in molecular biology techniques, forexample, to facilitate efficient insertion of a heterologous nucleicacid. The skilled person would readily recognize endonucleaserestriction sites such as XbaI and MluI. Engineered NDV vector genomecan also contain an L289A mutation in the fusion (F) protein forenhanced fusion, a self-cleaving hepatitis delta virus (HDV) ribozymesequence to ensure adherence to the “rule of six” by self-cleavingimmediately at the end of the viral antigenomic transcript, and a T7terminator sequence. An engineered NDV vector genome can also encode a Fprotein that has been mutated to contain a multi-basic cleavage site.The F protein and/or the HN protein of an engineered NDV vector genomecan be substituted with the corresponding avian paramyxovirus (APMV) Fprotein and/or HN protein, or part thereof. Modification of F, HN orboth, can be done using additional unique restriction endonuclease sitesthat flank these genes such as PacI, AgeI and AscI, which for examplehave been purposefully added in exemplified embodiments of thisdisclosure. When the substitution occurs in part, the resulting proteinwould be a chimeric protein, for example, a chimeric F protein and/or achimeric HN protein containing sequence from NDV and APMV. The APMV canbe APMV5.

The term “promoter,” as used herein, refers to a nucleotide sequencethat directs the transcription of a gene or coding sequence to which itis operably linked.

The term “operably linked”, as used herein, refers to an arrangement oftwo or more components, wherein the components so described are in arelationship permitting them to function in a coordinated manner. Forexample, a transcriptional regulatory sequence or a promoter is operablylinked to a coding sequence if the transcriptional regulatory sequenceor promoter facilitates aspects of the transcription of the codingsequence. The skilled person can readily recognize aspects of thetranscription process, which include, but not limited to, initiation,elongation, attenuation and termination. In general, an operably linkedtranscriptional regulatory sequence is joined in cis with the codingsequence, but it is not necessarily directly adjacent to it.

A “segment” of a nucleotide sequence is a sequence of contiguousnucleotides. A segment can be at least about 5, 10, 15, 20, 25, 30, 35,40, 45, 50, 60, 75, 85, 100, 110, 120, 130, 145, 150, 160, 175, 200,250, 300, 350, 400, 450, 500 or more contiguous nucleotides.

A “fragment” of an amino acid sequence is a sequence of contiguous aminoacids. A segment can be at least about 5, 10, 15, 20, 25, 30, 35, 40,45, 50, 60, 75, 85, 100, 110, 120, 130, 145, 150, 160, 175, 200, 250,300, 350, 400, 450, 500 or more contiguous amino acids.

The presence of the NDV vector genome can be tracked by a marker. Inanother embodiment, the NDV vector genome further comprises a nucleotidesequence encoding a marker. In another embodiment, the marker comprisesGFP.

A “therapeutic agent” can be an agent that can alleviate or reducesymptoms that result from an absence or defect in a protein in a cell,tissue or subject. In addition, a “therapeutic agent” can be an agentthat otherwise confers a benefit to a subject, e.g., anti-diseaseeffects or improvement in survivability upon exposure to a causativeagent of an infectious. A “therapeutic agent” can be a polypeptide, atherapeutic protein, an antigen, an antibody, or an antigen bindingfragment. The antibody can be a monoclonal, polyclonal, chimeric,humanized antibody, or a fragment thereof, or a combination thereof. Theantigen binding fragment is a Fab, Fab′, F(ab′)2, scFv, dsFv, ds-scFv,dimer, minibody, diabody, or multimer thereof or bispecific antibodyfragment, or a combination thereof. A “therapeutic agent” can be animmunogenic agent.

The term “immunogenic agent” as used herein refers to a molecule thatcan elicit an immune response in a subject. The immunogenic agent can bean antigenic molecule such as a polypeptide that can induce, forexample, humoral and/or cellular response, by activating B cells for theproduction of antibodies, CD4+ T cells for helper cell functions, andCD8+ T cells for their cytotoxic functions. An immunogenic agent can beencoded by a heterologous nucleic acid comprised in the engineered NDVvector or vaccine of the present disclosure. An immunogenic agent can bea protein or fragment thereof from an infectious agent for a disease,for example, such as influenza, SARS, MERS, or COVID-19.

SARS-CoV-2 is the causative agent of COVID-19. An immunogenic agent canbe, for example, the spike protein (also referred as “spike”) orfragment thereof of SARS-CoV-2. SARS-CoV-2 includes Variants of Concern(VoC) such as the South African B.1.351 variant (Peiris, M. and G. M.Leung, 2020). Other variants include variant B.1.1.7 having spikeprotein mutations delta69-70, delta144Y, N501Y, A570D, D614G, P681H,T716I, S982A, and D1118H; variant B.1.351 having spike protein mutationsL18F, D80A, D215G, delta241-243, R246I, K417N, E484K, N501Y, D614G, andA701V; and variant B.1.351 2P having spike protein mutation L18F, D80A,D215G, delta241-243, R246I, K417N, E484K, N501Y, D614G, A701V, andKV986-987PP. The spike protein can be modified to enhance itsstabilization. For example, proline mutations, such as two of F817P,A892P, A899P, A942P, K986P, and V987P, and in particular K986P and V987P(Hsieh, C.-L., et al., Science 2020), can be introduced to create apre-fusion stabilized spike protein immunogen, however, when there isonly 2 proline mutations, it is relatively unstable and difficult toproduce in mammalian cells. The present inventors found that when allsix prolines are introduced (i.e. when the engineered NDV expressesHexaPro (6 prolines)), version of prefusion stabilized spike, thatretains the prefusion conformation of the spike protein, is retained andit shows higher expression than only two prolines. The six proline spikeprotein can also withstand heating and freezing better than the twoprolines spike protein. In addition, the furin-cleavage site (RRAR) inthe spike protein can be mutated to GSAS to render it furin-cleavagedeficient, thereby increases its half-life. The immunogenic agent can befor priming and/or boosting an immune response against an antigen.Engineered NDV vectors of the present disclosure that express the spikeprotein include the constructs having the sequence in SEQ ID NO: 2-4, 18or 19, with those comprising the proline mutations and/or deficientfurin-cleavage site shown in SEQ ID NO: 18 and 19. In an embodiment, theengineered NDV vector comprising a nucleic acid having a nucleic acidsequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%,99.5%, 99.9% or 100% identical to the nucleic acid sequence any one ofSEQ ID NO: 2-4, 18, or 19. In an embodiment, the engineered NDV vectorcomprising a nucleic acid having a nucleic acid sequence that is atleast 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or 100%identical to the nucleic acid sequence of SEQ ID NO: 18 or 19. In anembodiment, the immunogenic agent is a SARS-CoV-2 spike protein orfragment thereof. In an embodiment, the SARS-CoV-2 spike protein isencoded by the nucleic acid sequence having at least 75%, 80%, 85%, 90%,95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100% identity to the nucleicacid sequence of SEQ ID NO: 8 or 17. In an embodiment, the SARS-CoV-2spike protein comprises an amino acid sequence having at least 85%, 90%,95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100% identity to the aminoacid sequence of SEQ ID NO: 6, 7, 29, 30, 31, or 41. In an embodiment,the SARS-CoV-2 spike protein comprises an amino acid sequence having atleast 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100% identityto a sequence of GenBank reference QHD43416.1 or QIZ15537.1, or variantB1.1.7 having spike protein mutations delta69-70, delta144Y, N501Y,A570D, D614G, P681H, T716I, S982A, D1118H, and L18F; variant B.1.351having spike protein mutations D80A, D215G, delta241-243, R246I, K417N,E484K, N501Y, D614G, and A701V; or variant B.1.351 2P having spikeprotein mutations L18F, D80A, D215G, delta241-243, R246I, K417N, E484K,N501Y, D614G, A701V, and KV986-987PP. In an embodiment, the SARS-CoV-2spike protein comprises an amino acid sequence having at least 85%, 90%,95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100% identity to a sequence ofGenBank reference QHD43416.1. In an embodiment, the SARS-CoV-2 spikeprotein comprises an amino acid sequence having at least 85%, 90%, 95%,96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100% identity to a sequence ofGenBank reference QIZ15537.1. In an embodiment, the SARS-CoV-2 spikeprotein comprises an amino acid sequence that is at least 85%, 90%, 95%,96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:6, 7, 29, 30, 31, or 41, comprising any two mutations selected from thegroup consisting of F817P, A892P, A899P, A942P, K986P, and V987P at thepositions corresponding to positions of SEQ ID NO: 6. In an embodiment,the mutations are K986P and V987P. In an embodiment, the SARS-CoV-2spike protein comprises an amino acid sequence that is at least 85%,90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence ofSEQ ID NO: 6, 7, 29, 30, 31, or 41, comprising mutations F817P, A892P,A899P, A942P, K986P, and V987P at the positions corresponding topositions of SEQ ID NO: 6. In an embodiment, the SARS-CoV-2 spikeprotein comprises an amino acid sequence that is at least 85%, 90%, 95%,96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:6, 7, 29, 30, 31, or 41, comprising mutations 682-RRAR-685 to682-GSAS-685, and any two mutations selected from the group consistingof F817P, A892P, A899P, A942P, K986P, and V987P at the positionscorresponding to positions of SEQ ID NO: 6. In an embodiment, themutations are K986P and V987P. In an embodiment, the SARS-CoV-2 spikeprotein comprises an amino acid sequence that is at least 85%, 90%, 95%,96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:6, 7, 29, 30, 31, or 41, comprising mutations 682-RRAR-685 to682-GSAS-685, F817P, A892P, A899P, A942P, K986P, and V987P at thepositions corresponding to positions of SEQ ID NO: 6. The term“pharmaceutically acceptable” in referring to diluent, buffer, carrier,or excipient, as used herein, includes any and all solvents, dispersionmedia, coatings, antibacterial and antifungal agents, isotonic andabsorption delaying agents, that are physiologically compatible.Pharmaceutically acceptable diluent, buffer, carrier, or excipientincludes sterile aqueous solutions or dispersions and sterile powdersfor the extemporaneous preparation of sterile injectable solutions ordispersion. The skilled person can readily recognize the use of suchmedia and agents for pharmaceutically active substances. In oneembodiment, the engineered NDV vector is comprised in a pharmaceuticalcomposition that includes a pharmaceutically acceptable diluent, buffer,carrier, or excipient.

The present inventors have provided an engineered Newcastle DiseaseVirus (NDV) vector comprising a nucleic acid comprises at least oneheterologous nucleic acid segment encoding a therapeutic agent operablylinked to a promoter capable of expressing the segment in a host cell.The present inventors have further provided a vaccine comprising anengineered NDV vector having a nucleic acid that comprises at least oneheterologous nucleic acid segment encoding an immunogenic agent operablylinked to a promoter capable of expressing the segment in a host cell,and methods of treating or preventing a disease, for example, aninfectious disease, with said vaccine or engineered NDV vector.

Accordingly, herein provided is an engineered NDV vector comprising anucleic acid having a nucleic acid sequence that is at least 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or 100% identical to thenucleic acid sequence of any one of SEQ ID NO: 1-5, 9, 10, 18, 19, 23,27, or 42, wherein the nucleic acid comprises a nucleic acid sequenceencoding an L protein having a stabilizing segment, wherein the nucleicacid comprises or further comprises at least one heterologous nucleicacid segment encoding a therapeutic agent operably linked to a promotercapable of expressing the segment in a host cell, and wherein thenucleic acid comprises XbaI and MluI restriction endonuclease sitesbetween nucleic acid sequence encoding phosphoprotein and matrixprotein. In an embodiment, the engineered NDV vector comprises a nucleicacid having a nucleic acid sequence that is at least 75%, 80%, 85%, 90%,95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or 100% identical to the nucleicacid sequence of SEQ ID NO: 9, 10, 23, or 27.

Also provided is an isolated nucleic acid having a nucleic acid sequencethat is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%,99.9% or 100% identical to the nucleic acid sequence of any one of SEQID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42, wherein the nucleic acidcomprises XbaI and MluI restriction endonuclease sites between nucleicacid sequence encoding phosphoprotein and matrix protein. In anembodiment, the isolated nucleic acid comprises a nucleic acid sequencethat is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%,99.9% or 100% identical to the nucleic acid sequence of SEQ ID NO: 9,10, 23, or 27.

In an embodiment, the at least one heterologous nucleic acid segmentencodes a therapeutic agent operably linked to a promoter capable ofexpressing the segment in a host cell.

In another aspect, also provided is an engineered chimeric NDV vectorcomprising a nucleic acid having a nucleic acid sequence encoding a Lprotein having a stabilizing segment, a chimeric F protein, and achimeric HN protein, wherein the chimeric F protein comprises avianparamyxovirus 5 (APMV5) F protein segment thereof at the N-terminus andan NDV F protein segment at the C-terminus, and wherein the chimeric HNprotein comprises an NDV HN protein segment at the N-terminus and anAMPV5 HN protein segment at the C-terminus. In an embodiment, thenucleic acid comprises XbaI and MluI restriction endonuclease sitesbetween nucleic acid sequence encoding phosphoprotein and matrixprotein. The stabilizing segment in L protein provides stability tomolecular clones in a host cell such as a bacterial cell. In anembodiment, the L protein comprises a stabilizing segment. In anembodiment, the L protein comprises an amino acid sequence having atleast 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100% identityto the amino acid sequence as set forth in SEQ ID NO: 11. In anembodiment, the stabilizing segment in the L protein comprises thesequence 1287-VSPYIHISNDSQRLFTEEGVKEGNVVYQQI-1316 (SEQ ID NO: 20). In anembodiment, the host cell is a bacterial cell.

The chimeric F protein is a chimeric with N-terminus APMV5 F protein andC-terminus NDV F protein, for example, NDV F protein from amino acidpositions 501 to 553 (SEQ ID NO: 28; encoded by SEQ ID NO: 32, i.e. Fgene in accession AF077761.1), which once incorporated into the chimericprotein become amino acid positions 494 to 546 in the chimeric protein,such as shown in SEQ ID NO: 12. In an embodiment, the chimeric F proteincomprises at the C-terminus 53 amino acids of NDV F protein from aminoacid positions 501 to 553 of SEQ ID NO: 28. In an embodiment, thechimeric F protein comprises an amino acid sequence having at least 85%,90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100% identity to theamino acid sequence of SEQ ID NO: 12. In an embodiment, the chimeric HNprotein comprises at the N-terminus 53 amino acids of NDV HN proteinfrom amino acid positions 1 to 53 of SEQ ID NO: 34. In an embodiment,the chimeric HN protein comprises an amino acid sequence having at least85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100% identity to theamino acid sequence of SEQ ID NO: 13. In an embodiment, the nucleic acidfurther comprises at least one heterologous nucleic acid segmentencoding a therapeutic agent operably linked to a promoter capable ofexpressing the segment in a host cell.

In an embodiment, the therapeutic agent comprises a SARS-CoV-2 spikeprotein or a fragment thereof. In an embodiment, the SARS-CoV-2 spikeprotein is encoded by the nucleic acid sequence having at least 75%,80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100% identityto the nucleic acid sequence of SEQ ID NO: 8 or 17. In an embodiment,the SARS-CoV-2 spike protein comprises an amino acid sequence having atleast 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100% identityto the amino acid sequence of SEQ ID NO: 6, 7, 29, 30, 31, or 41. In anembodiment, the SARS-CoV-2 spike protein comprises an amino acidsequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%,99.9%, or 100% identity to the amino acid sequence of GenBank referenceQHD43416.1 or QIZ15537.1, or variant B1.1.7 having spike proteinmutation of one or more of delta69-70, delta144Y, N501Y, A570D, D614G,P681H, T716I, S982A, D1118H, and L18F; variant B.1.351 having spikeprotein mutation of one or more of D80A, D215G, delta241-243, R246I,K417N, E484K, N501Y, D614G, and A701V; or variant B.1.351 2P havingspike protein mutation of one or more of L18F, D80A, D215G,delta241-243, R246I, K417N, E484K, N501Y, D614G, A701V, and KV986-987PP.In an embodiment, the SARS-CoV-2 spike protein comprises an amino acidsequence having a sequence of GenBank reference QHD43416.1. In anembodiment, the SARS-CoV-2 spike protein comprises an amino acidsequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%,99.9%, or 100% identity to the amino acid sequence of GenBank referenceQIZ15537.1. In an embodiment, the SARS-CoV-2 spike protein comprises anamino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or99% identical to the amino acid sequence of SEQ ID NO: 6, 7, 29, 30, 31,or 41, comprising any two mutations selected from the group consistingof F817P, A892P, A899P, A942P, K986P, and V987P at the positionscorresponding to positions of SEQ ID NO: 6. In an embodiment, theSARS-CoV-2 spike protein comprises an amino acid sequence that is atleast 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acidsequence of SEQ ID NO: 6, 7, 29, 30, 31, or 41, comprising mutationsF817P, A892P, A899P, A942P, K986P, and V987P at the positionscorresponding to positions of SEQ ID NO: 6. In an embodiment, theSARS-CoV-2 spike protein comprises an amino acid sequence having atleast 85%, 90%, 95%, 96%, 96%, 97%, 98%, or 99% identity to the aminoacid sequence of SEQ ID NO: 6, 7, 29, 30, 31, or 41, comprisingmutations 682-RRAR-685 to 682-GSAS-685, and any two mutations selectedfrom the group consisting of F817P, A892P, A899P, A942P, K986P, andV987P at the positions corresponding to positions of SEQ ID NO: 6. In anembodiment, the SARS-CoV-2 spike protein comprises an amino acidsequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identicalto the amino acid sequence of SEQ ID NO: 6, 7, 29, 30, 31, or 41,comprising mutations 682-RRAR-685 to 682-GSAS-685, F817P, A892P, A899P,A942P, K986P, and V987P at the positions corresponding to positions ofSEQ ID NO: 6.

The engineered NDV vector of the present disclosure can activate animmune response which is useful for its use as an immunogeniccomposition, an oncolytic agent, or a vaccine. Accordingly, alsoprovided is an immunogenic composition, an oncolytic agent, or avaccine, wherein the immunogenic composition, oncolytic agent, orvaccine comprises an engineered NDV vector comprising a nucleic acidhaving a nucleic acid sequence that is at least 75%, 80%, 85%, 90%, 95%,96%, 97%, 98%, 99%, 99.5%, 99.9% A or 100% identical to the nucleic acidsequence of any one of SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42,wherein the nucleic acid comprises a nucleic acid sequence encoding an Lprotein having a stabilizing segment, wherein the nucleic acid comprisesor further comprises at least one heterologous nucleic acid segmentencoding a therapeutic agent operably linked to a promoter capable ofexpressing the segment in a host cell, and wherein the nucleic acidcomprises XbaI and MluI restriction endonuclease sites between nucleicacid sequence encoding phosphoprotein and matrix protein. In someembodiments, the oncolytic agent comprises an engineered NDV vectorcomprising a nucleic acid having a nucleic acid sequence that is atleast 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or 100%identical to the nucleic acid sequence of any one of SEQ ID NO: 1-5, 9,10, 18, 19, 23, 27, or 42, wherein the nucleic acid comprises a nucleicacid sequence encoding an L protein having a stabilizing segment,wherein the nucleic acid comprises or further comprises at least oneheterologous nucleic acid segment encoding a therapeutic agent operablylinked to a promoter capable of expressing the segment in a host cell,and wherein the nucleic acid comprises XbaI and MluI restrictionendonuclease sites between nucleic acid sequence encoding phosphoproteinand matrix protein.

Also provided in the present disclosure is a pharmaceutical compositioncomprising an engineered NDV vector having a nucleic acid comprising anucleic acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%,97%, 98%, 99%, 99.5%, 99.9% or 100% identical to the nucleic acidsequence of any one of SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42, anda pharmaceutically acceptable carrier.

The engineered NDV vector, vaccine, immunogenic composition, orpharmaceutical composition described herein can be lyophilized withoutsignificant negative effects. In some embodiments, the engineered NDVvector, vaccine, immunogenic composition, or pharmaceutical compositionis lyophilized. In some embodiments, the lyophilized engineered NDVvector, vaccine, immunogenic composition, or pharmaceutical compositionis comprised in a solution comprising 1) 5% sucrose, 2) 5% sucrose and5% lodixanol, 3) 2.5% sucrose, 5% lactose, 1 peptone, 5 mM Tris-HCl, pH7.6, or 4) 2.5% sucrose, 2.5% lodixanol, 5% lactose, 1% peptone, 5 mMTris-HCl, pH 7.6, prior to lyophilization.

Nucleic acid and amino acid sequences described herein are set out inTable 1.

TABLE 1 Sequences SEQ ID NO:TAATACGACTCACTATAGGGACCAAACAGAGAATCCGTGAGTTACGATAAAAGGCGAAGG 1; nucleicAGCAATTGAAGTCGCACGGGTAGAAGGTGTGAATCTCGAGTGCGAGCCCGAAGCACAAAC sequence ofTCGAGAAAGCCTTCTGCCAACATGTCTTCCGTATTTGATGAGTACGAACAGCTCCTCGCG NDV-GFPGCTCAGACTCGCCCCAATGGAGCTCATGGAGGGGGAGAAAAAGGGAGTACCTTAAAAGTA MolecularGACGTCCCGGTATTCACTCTTAACAGTGATGACCCAGAAGATAGATGGAGCTTTGTGGTA CloneTTCTGCCTCCGGATTGCTGTTAGCGAAGATGCCAACAAACCACTCAGGCAAGGTGCTCTC AF077761.1_ATATCTCTTTTATGCTCCCACTCACAGGTAATGAGGAACCATGTTGCCATTGCAGGGAAA LaSota_KanCAGAATGAAGCCACATTGGCCGTGCTTGAGATTGATGGCTTTGCCAACGGCACGCCCCAG R (withTTCAACAATAGGAGTGGAGTGTCTGAAGAGAGAGCACAGAGATTTGCGATGATAGCAGGA stabilizingTCTCTCCCTCGGGCATGCAGCAACGGAACCCCGTTCGTCACAGCCGGGGCAGAAGATGAT sequence inGCACCAGAAGACATCACCGATACCCTGGAGAGGATCCTCTCTATCCAGGCTCAAGTATGG L)GTCACAGTAGCAAAAGCCATGACTGCGTATGAGACTGCAGATGAGTCGGAAACAAGGCGAATCAATAAGTATATGCAGCAAGGCAGGGTCCAAAAGAAATACATCCTCTACCCCGTATGCAGGAGCACAATCCAACTCACGATCAGACAGTCTCTTGCAGTCCGCATCTTTTTGGTTAGCGAGCTCAAGAGAGGCCGCAACACGGCAGGTGGTACCTCTACTTATTATAACCTGGTAGGGGACGTAGACTCATACATCAGGAATACCGGGCTTACTGCATTCTTCTTGACACTCAAGTACGGAATCAACACCAAGACATCAGCCCTTGCACTTAGTAGCCTCTCAGGCGACATCCAGAAGATGAAGCAGCTCATGCGTTTGTATCGGATGAAAGGAGATAATGCGCCGTACATGACATTACTTGGTGATAGTGACCAGATGAGCTTTGCGCCTGCCGAGTATGCACAACTTTACTCCTTTGCCATGGGTATGGCATCAGTCCTAGATAAAGGTACTGGGAAATACCAATTTGCCAGGGACTTTATGAGCACATCATTCTGGAGACTTGGAGTAGAGTACGCTCAGGCTCAGGGAAGTAGCATTAACGAGGATATGGCTGCCGAGCTAAAGCTAACCCCAGCAGCAATGAAGGGCCTGGCAGCTGCTGCCCAACGGGTCTCCGACGATACCAGCAGCATATACATGCCTACTCAACAAGTCGGAGTCCTCACTGGGCTTAGCGAGGGGGGGTCCCAAGCTCTACAAGGCGGATCGAATAGATCGCAAGGGCAACCAGAAGCCGGGGATGGGGAGACCCAATTCCTGGATCTGATGAGAGCGGTAGCAAATAGCATGAGGGAGGCGCCAAACTCTGCACAGGGCACTCCCCAATCGGGGCCTCCCCCAACTCCTGGGCCATCCCAAGATAACGACACCGACTGGGGGTATTGATGGACAAAACCCAGCCTGCTTCCACAAAAACATCCCAATGCCCTCACCCGTAGTCGACCCCTCGATTTGCGGCTCTATATGACCACACCCTCAAACAAACATCCCCCTCTTTCCTCCCTCCCCCTGCTGTACAACTCCGCACGCCCTAGATACCACAGGCACAATGCGGCTCACTAACAATCAAAACAGAGCCGAGGGAATTAGAAAAAAGTACGGGTAGAAGAGGGATATTCAGAGATCAGGGCAAGTCTCCCGAGTCTCTGCTCTCTCCTCTACCTGATAGACCAGGACAAACATGGCCACCTTTACAGATGCAGAGATCGACGAGCTATTTGAGACAAGTGGAACTGTCATTGACAACATAATTACAGCCCAGGGTAAACCAGCAGAGACTGTTGGAAGGAGTGCAATCCCACAAGGCAAGACCAAGGTGCTGAGCGCAGCATGGGAGAAGCATGGGAGCATCCAGCCACCGGCCAGTCAAGACAACCCCGATCGACAGGACAGATCTGACAAACAACCATCCACACCCGAGCAAACGACCCCGCATGACAGCCCGCCGGCCACATCCGCCGACCAGCCCCCCACCCAGGCCACAGACGAAGCCGTCGACACACAGTTCAGGACCGGAGCAAGCAACTCTCTGCTGTTGATGCTTGACAAGCTCAGCAATAAATCGTCCAATGCTAAAAAGGGCCCATGGTCGAGCCCCCAAGAGGGGAATCACCAACGTCCGACTCAACAGCAGGGGAGTCAACCCAGTCGCGGAAACAGTCAGGAAAGACCGCAGAACCAAGTCAAGGCCGCCCCTGGAAACCAGGGCACAGACGTGAACACAGCATATCATGGACAATGGGAGGAGTCACAACTATCAGCTGGTGCAACCCCTCATGCTCTCCGATCAAGGCAGAGCCAAGACAATACCCTTGTATCTGCGGATCATGTCCAGCCACCTGTAGACTTTGTGCAAGCGATGATGTCTATGATGGAGGCGATATCACAGAGAGTAAGTAAGGTTGACTATCAGCTAGATCTTGTCTTGAAACAGACATCCTCCATCCCTATGATGCGGTCCGAAATCCAACAGCTGAAAACATCTGTTGCAGTCATGGAAGCCAACTTGGGAATGATGAAGATTCTGGATCCCGGTTGTGCCAACATTTCATCTCTGAGTGATCTACGGGCAGTTGCCCGATCTCACCCGGTTTTAGTTTCAGGCCCTGGAGACCCCTCTCCCTATGTGACACAAGGAGGCGAAATGGCACTTAATAAACTTTCGCAACCAGTGCCACATCCATCTGAATTGATTAAACCCGCCACTGCATGCGGGCCTGATATAGGAGTGGAAAAGGACACTGTCCGTGCATTGATCATGTCACGCCCAATGCACCCGAGTTCTTCAGCCAAGCTCCTAAGCAAGTTAGATGCAGCCGGGTCGATCGAGGAAATCAGGAAAATCAAGCGCCTTGCTCTAAATGGCTAATTACTACTGCCACACGTAGCGGGTCCCTGTCCACTCGGCATCACACGGAATCTGCACCGAGTTCCCCCtctagaTTAGAAAAAATACGGGTAGAACCGCCACCATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCGCCCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAGTaATaaacgcgtACCCAAGGTCCAACTCTCCAAGCGGCAATCCTCTCTCGCTTCCTCAGCCCCACTGAATGGTCGCGTAACCGTAATTAATCTAGCTACATTTAAGATTAAGAAAAAATACGGGTAGAATTGGAGTGCCCCAATTGTGCCAAGATGGACTCATCTAGGACAATTGGGCTGTACTTTGATTCTGCCCATTCTTCTAGCAACCTGTTAGCATTTCCGATCGTCCTACAAGGCACAGGAGATGGGAAGAAGCAAATCGCCCCGCAATATAGGATCCAGCGCCTTGACTTGTGGACTGATAGTAAGGAGGACTCAGTATTCATCACCACCTATGGATTCATCTTTCAAGTTGGGAATGAAGAAGCCACTGTCGGCATGATCGATGATAAACCCAAGCGCGAGTTACTTTCCGCTGCGATGCTCTGCCTAGGAAGCGTCCCAAATACCGGAGACCTTATTGAGCTGGCAAGGGCCTGTCTCACTATGATAGTCACATGCAAGAAGAGTGCAACTAATACTGAGAGAATGGTTTTCTCAGTAGTGCAGGCACCCCAAGTGCTGCAAAGCTGTAGGGTTGTGGCAAACAAATACTCATCAGTGAATGCAGTCAAGCACGTGAAAGCGCCAGAGAAGATTCCCGGGAGTGGAACCCTAGAATACAAGGTGAACTTTGTCTCCTTGACTGTGGTACCGAAGAAGGATGTCTACAAGATCCCAGCTGCAGTATTGAAGGTTTCTGGCTCGAGTCTGTACAATCTTGCGCTCAATGTCACTATTAATGTGGAGGTAGACCCGAGGAGTCCTTTGGTTAAATCTTTGTCTAAGTCTGACAGCGGATACTATGCTAACCTCTTCTTGCATATTGGACTTATGACCACCGTAGATAGGAAGGGGAAGAAAGTGACATTTGACAAGCTGGAAAAGAAAATAAGGAGCCTTGATCTATCTGTCGGGCTCAGTGATGTGCTCGGGCCTTCCGTGTTGGTAAAAGCAAGAGGTGCACGGACTAAGCTTTTGGCACCTTTCTTCTCTAGCAGTGGGACAGCCTGCTATCCCATAGCAAATGCTTCTCCTCAGGTGGCCAAGATACTCTGGAGTCAAACCGCGTGCCTGCGGAGCGTTAAAATCATTATCCAAGCAGGTACCCAACGCGCTGTCGCAGTGACCGCCGACCACGAGGTTACCTCTACTAAGCTGGAGAAGGGGCACACCCTTGCCAAATACAATCCTTTTAAGAAATAAGCTGCGTCTCTGAGATTGCGCTCCGCCCACTCACCCAGATCATCATGACACAAAAAACTAATCTGTCTTGATTATTTACAGTTAGTTTACCTGTCTATCAAGTTAGAAAAAACACGGGTAGAAGATTCTGGATCCCGGTTGGCGCCCTCCAGGTGCAAGttaattaaATGGGCTCCAGACCTTCTACCAAGAACCCAGCACCTATGATGCTGACTATCCGGGTTGCGCTGGTACTGAGTTGCATCTGTCCGGCAAACTCCATTGATGGCAGGCCTCTTGCAGCTGCAGGAATTGTGGTTAGAGGAGACAAAGCCGTCAACATATACACCTCATCCCAGACAGGATCAATCATAGTTAAGCTCCTCCCGAATCTGCCCAAGGATAAGGAGGCATGTGCGAAAGCCCCCTTGGATGCATACAACAGGACATTGACCACTTTGCTCACCCCCCTTGGTGACTCTATCCGTAGGATACAAGAGTCTGTGACTACATCTGGAGGGGGGAGACAGGGGCGCCTTATAGGCGCCATTATTGGCGGTGTGGCTCTTGGGGTTGCAACTGCCGCACAAATAACAGCGGCCGCAGCTCTGATACAAGCCAAACAAAATGCTGCCAACATCCTCCGACTTAAAGAGAGCATTGCCGCAACCAATGAGGCTGTGCATGAGGTCACTGACGGATTATCGCAACTAGCAGTGGCAGTTGGGAAGATGCAGCAGTTTGTTAATGACCAATTTAATAAAACAGCTCAGGAATTAGACTGCATCAAAATTGCACAGCAAGTTGGTGTAGAGCTCAACCTGTACCTAACCGAATTGACTACAGTATTCGGACCACAAATCACTTCACCTGCTTTAAACAAGCTGACTATTCAGGCACTTTACAATCTAGCTGGTGGAAATATGGATTACTTATTGACTAAGTTAGGTGTAGGGAACAATCAACTCAGCTCATTAATCGGTAGCGGCTTAATCACtGGCAACCCTATTCTATACGACTCACAGACTCAACTCTTGGGTATACAGGTAACTgcaCCTTCAGTCGGGAACCTAAATAATATGCGTGCCACCTACTTGGAAACCTTATCCGTAAGCACAACCAGGGGATTTGCCTCGGCACTTGTCCCCAAAGTGGTGACACAGGTCGGTTCTGTGATAGAAGAACTTGACACCTCATACTGTATAGAAACTGACTTAGATTTATATTGTACAAGAATAGTAACGTTCCCTATGTCCCCTGGTATTTATTCCTGCTTGAGCGGCAATACGTCGGCCTGTATGTACTCAAAGACCGAAGGCGCACTTACTACACCATACATGACTATCAAAGGTTCAGTCATCGCCAACTGCAAGATGACAACATGTAGATGTGTAAACCCCCCGGGTATCATATCGCAAAACTATGGAGAAGCCGTGTCTCTAATAGATAAACAATCATGCAATGTTTTATCCTTAGGCGGGATAACTTTAAGGCTCAGTGGGGAATTCGATGTAACTTATCAGAAGAATATCTCAATACAAGATTCTCAAGTAATAATAACAGGCAATCTTGATATCTCAACTGAGCTTGGGAATGTCAACAACTCGATCAGTAATGCTTTGAATAAGTTAGAGGAAAGCAACAGAAAACTAGACAAAGTCAATGTCAAACTGACTAGCACATCTGCTCTCATTACgTATATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTGATTCTAGCATGCTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTTATTATGGCTTGGGAATAATACaCTcGATCAGATGAGAGCCACTACAAAAATGTGAACACAGATGAGGAACGAAGGTTTCCCTAATAGTAATTTGTGTGAAAGTTCTGGTAGTCTGTCAGTTCAGAGAGTTAAGAAAAAACTACCGGTTGTAGATGACCAAAGGACGATATACGGGTAGAACGGTAAGAGAGGCCGCCCCTCAATTGCGAGCCAGGCTTCACAACCTCCGTTCTACCGCTTCACCGACAACAGTCCTCAATCATGGACCGCGCCGTTAGCCAAGTTGCGTTAGAGAATGATGAAAGAGAGGCAAAAAATACATGGCGCTTGATATTCCGGATTGCAATCTTATTCTTAACAGTAGTGACCTTGGCTATATCTGTAGCCTCCCTTTTATATAGCATGGGGGCTAGCACACCTAGCGATCTTGTAGGCATACCGACTAGGATTTCCAGGGCAGAAGAAAAGATTACATCTACACTTGGTTCCAATCAAGATGTAGTAGATAGGATATATAAGCAAGTGGCCCTTGAGTCTCCGTTGGCATTGTTAAATACTGAGACCACAATTATGAACGCAATAACATCTCTCTCTTATCAGATTAATGGAGCTGCAAACAACAGTGGGTGGGGGGCACCTATCCATGACCCAGATTATATAGGGGGGATAGGCAAAGAACTCATTGTAGATGATGCTAGTGATGTCACATCATTCTATCCCTCTGCATTTCAAGAACATCTGAATTTTATCCCGGCGCCTACTACAGGATCAGGTTGCACTCGAATACCCTCATTTGACATGAGTGCTACCCATTACTGCTACACCCATAATGTAATATTGTCTGGATGCAGAGATCACTCACATTCATATCAGTATTTAGCACTTGGTGTGCTCCGGACATCTGCAACAGGGAGGGTATTCTTTTCTACTCTGCGTTCCATCAACCTGGACGACACCCAAAATCGGAAGTCTTGCAGTGTGAGTGCAACTCCCCTGGGTTGTGATATGCTGTGCTCGAAAGTCACGGAGACAGAGGAAGAAGATTATAACTCAGCTGTCCCTACGCGGATGGTACATGGGAGGTTAGGGTTCGACGGCCAGTACCACGAAAAGGACCTAGATGTCACAACATTATTCGGGGACTGGGTGGCCAACTACCCAGGAGTAGGGGGTGGATCTTTTATTGACAGCCGCGTATGGTTCTCAGTCTACGGAGGGTTAAAACCCAATTCACCCAGTGACACTGTACAGGAAGGGAAATATGTGATATACAAGCGATACAATGACACATGCCCAGATGAGCAAGACTACCAGATTCGAATGGCCAAGTCTTCGTATAAGCCTGGACGGTTTGGTGGGAAACGCATACAGCAGGCTATCTTATCTATCAAGGTGTCAACATCCTTAGGCGAAGACCCGGTACTGACTGTACCGCCCAACACAGTCACACTCATGGGGGCCGAAGGCAGAATTCTCACAGTAGGGACATCTCATTTCTTGTATCAACGAGGGTCATCATACTTCTCTCCCGCGTTATTATATCCTATGACAGTCAGCAACAAAACAGCCACTCTTCATAGTCCTTATACATTCAATGCCTTCACTCGGCCAGGTAGTATCCCTTGCCAGGCTTCAGCAAGATGCCCCAACTCGTGTGTTACTGGAGTCTATACAGATCCATATCCCCTAATCTTCTATAGAAACCACACCTTGCGAGGGGTATTCGGGACAATGCTTGATGGTGTACAAGCAAGACTTAACCCTGCGTCTGCAGTATTCGATAGCACATCCCGCAGTCGCATTACTCGAGTGAGTTCAAGCAGTACCAAAGCAGCATACACAACATCAACTTGTTTTAAAGTGGTCAAGACTAATAAGACCTATTGTCTCAGCATTGCTGAAATATCTAATACTCTCTTCGGAGAATTCAGAATCGTCCCGTTACTAGTTGAGATCCTCAAAGATGACGGGGTTAGAGAAGCCAGGTCTGGCTAGggcgcgccTTGAGTCAATTATAAAGGAGTTGGAAAGATGGCATTGTATCACCTATCTTCTGCGACATCAAGAATCAAACCGAATGCCGGCGCGTGCTCGAATTCCATGTTGCCAGTTGACCACAATCAGCCAGTGCTCATGCGATCAGATTAAGCCTTGTCATTAATCTCTTGATTAAGAAAAAATGTAAGTGGCAATGAGATACAAGGCAAAACAGCTCATGGTAAATAATACGGGTAGGACATGGCGAGCTCCGGTCCTGAAAGGGCAGAGCATCAGATTATCCTACCAGAGCCACACCTGTCTTCACCATTGGTCAAGCACAAACTACTCTATTACTGGAAATTAACTGGGCTACCGCTTCCTGATGAATGTGACTTCGACCACCTCATTCTCAGCCGACAATGGAAAAAAATACTTGAATCGGCCTCTCCTGATACTGAGAGAATGATAAAACTCGGAAGGGCAGTACACCAAACTCTTAACCACAATTCCAGAATAACCGGAGTGCTCCACCCCAGGTGTTTAGAACAACTGGCTAATATTGAGGTCCCAGATTCAACCAACAAATTTCGGAAGATTGAGAAGAAGATCCAAATTCACAACACGAGATATGGAGAACTGTTCACAAGGCTGTGTACGCATATAGAGAAGAAACTGCTGGGGTCATCTTGGTCTAACAATGTCCCCCGGTCAGAGGAGTTCAGCAGCATTCGTACGGATCCGGCATTCTGGTTTCACTCAAAATGGTCCACAGCCAAGTTTGCATGGCTCCATATAAAACAGATCCAGAGGCATCTGATGGTGGCAGCTAAGACAAGGTCTGCGGCCAACAAATTGGTGATGCTAACCCATAAGGTAGGCCAAGTCTTTGTCACTCCTGAACTTGTCGTTGTGACGCATACGAATGAGAACAAGTTCACATGTCTTACCCAGGAACTTGTATTGATGTATGCAGATATGATGGAGGGCAGAGATATGGTCAACATAATATCAACCACGGCGGTGCATCTCAGAAGCTTATCAGAGAAAATTGATGACATTTTGCGGTTAATAGACGCTCTGGCAAAAGACTTGGGTAATCAAGTCTACGATGTTGTATCACTAATGGAGGGATTTGCATACGGAGCTGTCCAGCTACTCGAGCCGTCAGGTACATTTGCAGGAGATTTCTTCGCATTCAACCTGCAGGAGCTTAAAGACATTCTAATTGGCCTCCTCCCCAATGATATAGCAGAATCCGTGACTCATGCAATCGCTACTGTATTCTCTGGTTTAGAACAGAATCAAGCAGCTGAGATGTTGTGTCTGTTGCGTCTGTGGGGTCACCCACTGCTTGAGTCCCGTATTGCAGCAAAGGCAGTCAGGAGCCAAATGTGCGCACCGAAAATGGTAGACTTTGATATGATCCTTCAGGTACTGTCTTTCTTCAAGGGAACAATCATCAACGGGTACAGAAAGAAGAATGCAGGTGTGTGGCCGCGAGTCAAAGTGGATACAATATATGGGAAGGTCATTGGGCAACTACATGCAGATTCAGCAGAGATTTCACACGATATCATGTTGAGAGAGTATAAGAGTTTATCTGCACTTGAATTTGAGCCATGTATAGAATATGACCCTGTCACCAACCTGAGCATGTTCCTAAAAGACAAGGCAATCGCACACCCCAACGATAATTGGCTTGCCTCGTTTAGGCGGAACCTTCTCTCCGAAGACCAGAAGAAACATGTAAAAGAAGCAACTTCGACTAATCGCCTCTTGATAGAGTTTTTAGAGTCAAATGATTTTGATCCATATAAAGAGATGGAATATCTGACGACCCTTGAGTACCTTAGAGATGACAATGTGGCAGTATCATACTCGCTCAAGGAGAAGGAAGTGAAAGTTAATGGACGGATCTTCGCTAAGCTGACAAAGAAGTTAAGGAACTGTCAGGTGATGGCGGAAGGGATCCTAGCCGATCAGATTGCACCTTTCTTTCAGGGAAATGGAGTCATTCAGGATAGCATATCCTTGACCAAGAGTATGCTAGCGATGAGTCAACTGTCTTTTAACAGCAATAAGAAACGTATCACTGACTGTAAAGAAAGAGTATCTTCAAACCGCAATCATGATCCGAAAAGCAAGAACCGTCGGAGAGTTGCAACCTTCATAACAACTGACCTGCAAAAGTACTGTCTTAATTGGAGATATCAGACAATCAAATTGTTCGCTCATGCCATCAATCAGTTGATGGGCCTACCTCACTTCTTCGAATGGATTCACCTAAGACTGATGGACACTACGATGTTCGTAGGAGACCCTTTCAATCCTCCAAGTGACCCTACTGACTGTGACCTCTCAAGAGTCCCTAATGATGACATATATATTGTCAGTGCCAGAGGGGGTATCGAAGGATTATGCCAGAAGCTATGGACAATGATCTCAATTGCTGCAATCCAACTTGCTGCAGCTAGATCGCATTGTCGTGTTGCCTGTATGGTACAGGGTGATAATCAAGTAATAGCAGTAACGAGAGAGGTAAGATCAGACGACTCTCCGGAGATGGTGTTGACACAGTTGCATCAAGCCAGTGATAATTTCTTCAAGGAATTAATTCATGTCAATCATTTGATTGGCCATAATTTGAAGGATCGTGAAACCATCAGGTCAGACACATTCTTCATATACAGCAAACGAATCTTCAAAGATGGAGCAATCCTCAGTCAAGTCCTCAAAAATTCATCTAAATTAGTGCTAGTGTCAGGTGATCTCAGTGAAAACACCGTAATGTCCTGTGCCAACATTGCCTCTACTGTAGCACGGCTATGCGAGAACGGGCTTCCCAAAGACTTCTGTTACTATTTAAACTATATAATGAGTTGTGTGCAGACATACTTTGACTCTGAGTTCTCCATCACCAACAATTCGCACCCCGATCTTAATCAGTCGTGGATTGAGGACATCTCTTTTGTGCACTCATATGTTCTGACTCCTGCCCAATTAGGGGGACTGAGTAACCTTCAATACTCAAGGCTCTACACTAGAAATATCGGTGACCCGGGGACTACTGCTTTTGCAGAGATCAAGCGACTAGAAGCAGTGGGATTACTGAGTCCTAACATTATGACTAATATCTTAACTAGGCCGCCTGGGAATGGAGATTGGGCCAGTCTGTGCAACGACCCATACTCTTTCAATTTTGAGACTGTTGCAAGCCCAAATATTGTTCTTAAGAAACATACGCAAAGAGTCCTATTTGAAACTTGTTCAAATCCCTTATTGTCTGGAGTGCACACAGAGGATAATGAGGCAGAAGAGAAGGCATTGGCTGAATTCTTGCTTAATCAAGAGGTGATTCATCCCCGCGTTGCGCATGCCATCATGGAGGCAAGCTCTGTAGGTAGGAGAAAGCAAATTCAAGGGCTTGTTGACACAACAAACACCGTAATTAAGATTGCGCTTACTAGGAGGCCATTAGGCATCAAGAGGCTGATGCGGATAGTCAATTATTCTAGCATGCATGCAATGCTGTTTAGAGACGATGTTTTTTCCTCCAGTAGATCCAACCACCCCTTAGTCTCTTCTAATATGTGTTCTCTGACACTGGCAGACTATGCACGGAATAGAAGCTGGTCACCTTTGACGGGAGGCAGGAAAATACTGGGTGTATCTAATCCTGATACGATAGAACTCGTAGAGGGTGAGATTCTTAGTGTAAGCGGAGGGTGTACAAGATGTGACAGCGGAGATGAACAATTTACTTGGTTCCATCTTCCAAGCAATATAGAATTGACCGATGACACCAGCAAGAATCCTCCGATGAGGGTACCATATCTCGGGTCAAAGACACAGGAGAGGAGAGCTGCCTCACTTGCAAAAATAGCTCATATGTCGCCACATGTAAAGGCTGCCCTAAGGGCATCATCCGTGTTGATCTGGGCTTATGGGGATAATGAAGTAAATTGGACTGCTGCTCTTACGATTGCAAAATCTCGGTGTAATGTAAACTTAGAGTATCTTCGGTTACTGTCCCCTTTACCCACGGCTGGGAATCTTCAACATAGACTAGATGATGGTATAACTCAGATGACATTCACCCCTGCATCTCTCTACAGGgtgtcaccttacattcacatatccaatgattctcaaaggctgttcactgaagaaggagtcaaagaggggaatgtggtttaccaacagatcATGCTCTTGGGTTTATCTCTAATCGAATCGATCTTTCCAATGACAACAACCAGGACATATGATGAGATCACACTGCACCTACATAGTAAATTTAGTTGCTGTATCAGAGAAGCACCTGTTGCGGTTCCTTTCGAGCTACTTGGGGTGGTACCGGAACTGAGGACAGTGACCTCAAATAAGTTTATGTATGATCCTAGCCCTGTATCGGAGGGAGACTTTGCGAGACTTGACTTAGCTATCTTCAAGAGTTATGAGCTTAATCTGGAGTCATATCCCACGATAGAGCTAATGAACATTCTTTCAATATCCAGCGGGAAGTTGATTGGCCAGTCTGTGGTTTCTTATGATGAAGATACCTCCATAAAGAATGACGCCATAATAGTGTATGACAATACCCGAAATTGGATCAGTGAAGCTCAGAATTCAGATGTGGTCCGCCTATTTGAATATGCAGCACTTGAAGTGCTCCTCGACTGTTCTTACCAACTCTATTACCTGAGAGTAAGAGGCCTAGACAATATTGTCTTATATATGGGTGATTTATACAAGAATATGCCAGGAATTCTACTTTCCAACATTGCAGCTACAATATCTCATCCCGTCATTCATTCAAGGTTACATGCAGTGGGCCTGGTCAACCATGACGGATCACACCAACTTGCAGATACGGATTTTATCGAAATGTCTGCAAAACTATTAGTATCTTGCACCCGACGTGTGATCTCCGGCTTATATTCAGGAAATAAGTATGATCTGCTGTTCCCATCTGTCTTAGATGATAACCTGAATGAGAAGATGCTTCAGCTGATATCCCGGTTATGCTGTCTGTACACGGTACTCTTTGCTACAACAAGAGAAATCCCGAAAATAAGAGGCTTAACTGCAGAAGAGAAATGTTCAATACTCACTGAGTATTTACTGTCGGATGCTGTGAAACCATTACTTAGCCCCGATCAAGTGAGCTCTATCATGTCTCCTAACATAATTACATTCCCAGCTAATCTGTACTACATGTCTCGGAAGAGCCTCAATTTGATCAGGGAAAGGGAGGACAGGGATACTATCCTGGCGTTGTTGTTCCCCCAAGAGCCATTATTAGAGTTCCCTTCTGTGCAAGATATTGGTGCTCGAGTGAAAGATCCATTCACCCGACAACCTGCGGCATTTTTGCAAGAGTTAGATTTGAGTGCTCCAGCAAGGTATGACGCATTCACACTTAGTCAGATTCATCCTGAACTCACATCTCCAAATCCGGAGGAAGACTACTTAGTACGATACTTGTTCAGAGGGATAGGGACTGCATCTTCCTCTTGGTATAAGGCATCTCATCTCCTTTCTGTACCCGAGGTAAGATGTGCAAGACACGGGAACTCCTTATACTTAGCTGAAGGGAGCGGAGCCATCATGAGTCTTCTCGAACTGCATGTACCACATGAAACTATCTATTACAATACGCTCTTTTCAAATGAGATGAACCCCCCGCAACGACATTTCGGGCCGACCCCAACTCAGTTTTTGAATTCGGTTGTTTATAGGAATCTACAGGCGGAGGTAACATGCAAAGATGGATTTGTCCAAGAGTTCCGTCCATTATGGAGAGAAAATACAGAGGAAAGTGACCTGACCTCAGATAAAGCAGTGGGGTATATTACATCTGCAGTGCCCTACAGATCTGTATCATTGCTGCATTGTGACATTGAAATTCCTCCAGGGTCCAATCAAAGCTTACTAGATCAACTAGCTATCAATTTATCTCTGATTGCCATGCATTCTGTAAGGGAGGGCGGGGTAGTAATCATCAAAGTGTTGTATGCAATGGGATACTACTTTCATCTACTCATGAACTTGTTTGCTCCGTGTTCCACAAAAGGATATATTCTCTCTAATGGTTATGCATGTCGAGGAGATATGGAGTGTTACCTGGTATTTGTCATGGGTTACCTGGGCGGGCCTACATTTGTACATGAGGTGGTGAGGATGGCAAAAACTCTGGTGCAGCGGCACGGTACGCTCTTGTCTAAATCAGATGAGATCACACTGACCAGGTTATTCACCTCACAGCGGCAGCGTGTGACAGACATCCTATCCAGTCCTTTACCAAGATTAATAAAGTACTTGAGGAAGAATATTGACACTGCGCTGATTGAAGCCGGGGGACAGCCCGTCCGTCCATTCTGTGCGGAGAGTCTGGTGAGCACGCTAGCGAACATAACTCAGATAACCCAGATTATCGCTAGTCACATTGACACAGTTATCCGGTCTGTGATATATATGGAAGCTGAGGGTGATCTCGCTGACACAGTATTTCTATTTACCCCTTACAATCTCTCTACTGACGGGAAAAAGAGGACATCACTTATACAGTGCACGAGACAGATCCTAGAGGTTACAATACTAGGTCTTAGAGTCGAAAATCTCAATAAAATAGGCGATATAATCAGCCTAGTGCTTAAAGGCATGATCTCCATGGAGGACCTTATCCCACTAAGGACATACTTGAAGCATAGTACCTGCCCTAAATATTTGAAGGCTGTCCTAGGTATTACCAAACTCAAAGAAATGTTTACAGACACTTCTGTATTGTACTTGACTCGTGCTCAACAAAAATTCTACATGAAAACTATAGGCAATGCAGTCAAAGGATATTACAGTAACTGTGACTCTTAACGAAAATCACATATTAATAGGCTCCTTTTTTGGCCAATTGTATTCTTGTTGATTTAATCATATTATGTTAGAAAAAAGTTGAACCCTGACTCCTTAGGACTCGAATTCGAACTCAAATAAATGTCTTAAAAAAAGGTTGCGCACAATTATTCTTGAGTGTAGTCTCGTCATTCACCAAATCTTTGTTTGGTGGCCGGCATGGTCCCAGCCTCCTCGCTGGCGCCGGCTGGGCAACATTCCGAGGGGACCGTCCCCTCGGTAATGGCGAATGGGACGTCGACTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTATAT SEQ ID NO:TAATACGACTCACTATAGGGACCAAACAGAGAATCCGTGAGTTACGATAAAAGGCGAAGG2; nucleotideAGCAATTGAAGTCGCACGGGTAGAAGGTGTGAATCTCGAGTGCGAGCCCGAAGCACAAAC sequence ofTCGAGAAAGCCTTCTGCCAACATGTCTTCCGTATTTGATGAGTACGAACAGCTCCTCGCG NDV-FLSGCTCAGACTCGCCCCAATGGAGCTCATGGAGGGGGAGAAAAAGGGAGTACCTTAAAAGTA MolecularGACGTCCCGGTATTCACTCTTAACAGTGATGACCCAGAAGATAGATGGAGCTTTGTGGTA CloneTTCTGCCTCCGGATTGCTGTTAGCGAAGATGCCAACAAACCACTCAGGCAAGGTGCTCTC AF077761.1_ATATCTCTTTTATGCTCCCACTCACAGGTAATGAGGAACCATGTTGCCATTGCAGGGAAA LaSota_KanCAGAATGAAGCCACATTGGCCGTGCTTGAGATTGATGGCTTTGCCAACGGCACGCCCCAG R (withTTCAACAATAGGAGTGGAGTGTCTGAAGAGAGAGCACAGAGATTTGCGATGATAGCAGGA stabilizingTCTCTCCCTCGGGCATGCAGCAACGGAACCCCGTTCGTCACAGCCGGGGCAGAAGATGAT sequence inGCACCAGAAGACATCACCGATACCCTGGAGAGGATCCTCTCTATCCAGGCTCAAGTATGG L)GTCACAGTAGCAAAAGCCATGACTGCGTATGAGACTGCAGATGAGTCGGAAACAAGGCGAATCAATAAGTATATGCAGCAAGGCAGGGTCCAAAAGAAATACATCCTCTACCCCGTATGCAGGAGCACAATCCAACTCACGATCAGACAGTCTCTTGCAGTCCGCATCTTTTTGGTTAGCGAGCTCAAGAGAGGCCGCAACACGGCAGGTGGTACCTCTACTTATTATAACCTGGTAGGGGACGTAGACTCATACATCAGGAATACCGGGCTTACTGCATTCTTCTTGACACTCAAGTACGGAATCAACACCAAGACATCAGCCCTTGCACTTAGTAGCCTCTCAGGCGACATCCAGAAGATGAAGCAGCTCATGCGTTTGTATCGGATGAAAGGAGATAATGCGCCGTACATGACATTACTTGGTGATAGTGACCAGATGAGCTTTGCGCCTGCCGAGTATGCACAACTTTACTCCTTTGCCATGGGTATGGCATCAGTCCTAGATAAAGGTACTGGGAAATACCAATTTGCCAGGGACTTTATGAGCACATCATTCTGGAGACTTGGAGTAGAGTACGCTCAGGCTCAGGGAAGTAGCATTAACGAGGATATGGCTGCCGAGCTAAAGCTAACCCCAGCAGCAATGAAGGGCCTGGCAGCTGCTGCCCAACGGGTCTCCGACGATACCAGCAGCATATACATGCCTACTCAACAAGTCGGAGTCCTCACTGGGCTTAGCGAGGGGGGGTCCCAAGCTCTACAAGGCGGATCGAATAGATCGCAAGGGCAACCAGAAGCCGGGGATGGGGAGACCCAATTCCTGGATCTGATGAGAGCGGTAGCAAATAGCATGAGGGAGGCGCCAAACTCTGCACAGGGCACTCCCCAATCGGGGCCTCCCCCAACTCCTGGGCCATCCCAAGATAACGACACCGACTGGGGGTATTGATGGACAAAACCCAGCCTGCTTCCACAAAAACATCCCAATGCCCTCACCCGTAGTCGACCCCTCGATTTGCGGCTCTATATGACCACACCCTCAAACAAACATCCCCCTCTTTCCTCCCTCCCCCTGCTGTACAACTCCGCACGCCCTAGATACCACAGGCACAATGCGGCTCACTAACAATCAAAACAGAGCCGAGGGAATTAGAAAAAAGTACGGGTAGAAGAGGGATATTCAGAGATCAGGGCAAGTCTCCCGAGTCTCTGCTCTCTCCTCTACCTGATAGACCAGGACAAACATGGCCACCTTTACAGATGCAGAGATCGACGAGCTATTTGAGACAAGTGGAACTGTCATTGACAACATAATTACAGCCCAGGGTAAACCAGCAGAGACTGTTGGAAGGAGTGCAATCCCACAAGGCAAGACCAAGGTGCTGAGCGCAGCATGGGAGAAGCATGGGAGCATCCAGCCACCGGCCAGTCAAGACAACCCCGATCGACAGGACAGATCTGACAAACAACCATCCACACCCGAGCAAACGACCCCGCATGACAGCCCGCCGGCCACATCCGCCGACCAGCCCCCCACCCAGGCCACAGACGAAGCCGTCGACACACAGTTCAGGACCGGAGCAAGCAACTCTCTGCTGTTGATGCTTGACAAGCTCAGCAATAAATCGTCCAATGCTAAAAAGGGCCCATGGTCGAGCCCCCAAGAGGGGAATCACCAACGTCCGACTCAACAGCAGGGGAGTCAACCCAGTCGCGGAAACAGTCAGGAAAGACCGCAGAACCAAGTCAAGGCCGCCCCTGGAAACCAGGGCACAGACGTGAACACAGCATATCATGGACAATGGGAGGAGTCACAACTATCAGCTGGTGCAACCCCTCATGCTCTCCGATCAAGGCAGAGCCAAGACAATACCCTTGTATCTGCGGATCATGTCCAGCCACCTGTAGACTTTGTGCAAGCGATGATGTCTATGATGGAGGCGATATCACAGAGAGTAAGTAAGGTTGACTATCAGCTAGATCTTGTCTTGAAACAGACATCCTCCATCCCTATGATGCGGTCCGAAATCCAACAGCTGAAAACATCTGTTGCAGTCATGGAAGCCAACTTGGGAATGATGAAGATTCTGGATCCCGGTTGTGCCAACATTTCATCTCTGAGTGATCTACGGGCAGTTGCCCGATCTCACCCGGTTTTAGTTTCAGGCCCTGGAGACCCCTCTCCCTATGTGACACAAGGAGGCGAAATGGCACTTAATAAACTTTCGCAACCAGTGCCACATCCATCTGAATTGATTAAACCCGCCACTGCATGCGGGCCTGATATAGGAGTGGAAAAGGACACTGTCCGTGCATTGATCATGTCACGCCCAATGCACCCGAGTTCTTCAGCCAAGCTCCTAAGCAAGTTAGATGCAGCCGGGTCGATCGAGGAAATCAGGAAAATCAAGCGCCTTGCTCTAAATGGCTAATTACTACTGCCACACGTAGCGGGTCCCTGTCCACTCGGCATCACACGGAATCTGCACCGAGTTCCCCCtctagaTTAGAAAAAATACGGGTAGAACCGCCACCATGTTCGTGTTCCTGGTCCTGCTGCCACTGGTAAGCTCCCAATGTGTAAACTTAACCACAAGAACCCAGCTCCCACCTGCCTACACCAACAGCTTCACCAGAGGCGTTTATTACCCCGACAAGGTATTCCGGTCTTCTGTTCTGCACTCTACCCAGGACCTGTTTCTGCCCTTTTTCAGCAACGTGACATGGTTCCACGCCATCCACGTGTCTGGCACAAACGGCACCAAGCGGTTTGATAATCCTGTGCTCCCTTTCAATGACGGCGTGTACTTCGCCTCTACTGAGAAGAGCAACATCATCCGGGGCTGGATCTTTGGCACAACACTGGACTCTAAAACCCAGAGCCTGCTGATCGTGAACAACGCCACCAACGTGGTGATTAAGGTGTGCGAGTTCCAGTTCTGCAATGACCCTTTCCTCGGCGTGTACTACCACAAGAACAACAAAAGTTGGATGGAAAGCGAATTCAGGGTGTACTCAAGCGCCAACAACTGTACCTTCGAGTACGTGAGCCAGCCTTTCCTGATGGACCTAGAAGGTAAGCAGGGCAATTTCAAGAACCTCAGAGAGTTCGTGTTCAAGAATATTGACGGCTACTTCAAAATCTACAGCAAGCACACCCCAATCAACCTGGTGCGGGACCTGCCCCAGGGCTTTAGCGCGCTGGAGCCTCTGGTGGACCTGCCTATCGGCATCAACATCACCCGGTTCCAGACACTGCTGGCTCTGCATAGAAGCTACCTGACACCTGGCGACAGTTCTTCTGGCTGGACAGCCGGCGCCGCCGCCTACTACGTGGGCTACCTGCAGCCTAGAACATTCCTGCTGAAATACAACGAGAACGGCACGATCACAGACGCCGTGGACTGCGCCCTGGATCCCCTGTCTGAGACAAAGTGCACCCTGAAGTCTTTCACCGTGGAGAAGGGCATCTACCAGACCTCCAACTTCAGAGTGCAGCCTACCGAATCCATCGTGCGCTTTCCCAACATCACCAACCTGTGCCCCTTCGGCGAGGTCTTTAATGCCACGAGATTCGCCAGCGTGTATGCCTGGAACAGAAAGAGAATCAGCAACTGCGTGGCCGACTACAGCGTGCTGTACAACAGCGCCTCTTTCAGCACATTTAAGTGCTACGGAGTGTCTCCTACCAAACTCAACGATCTGTGCTTCACGAACGTGTATGCCGACAGCTTCGTGATCCGAGGAGATGAGGTGCGGCAGATCGCTCCAGGACAGACAGGCAAGATCGCCGACTACAACTACAAGCTGCCCGACGACTTTACCGGCTGCGTGATCGCTTGGAACAGCAATAACCTGGACTCAAAGGTTGGAGGAAACTACAACTACCTGTACAGACTGTTCAGAAAGTCCAACCTGAAGCCCTTCGAGAGAGACATCTCTACAGAAATCTACCAGGCCGGCAGCACCCCATGTAACGGCGTGGAAGGCTTCAACTGCTACTTCCCTCTGCAGTCTTATGGCTTCCAGCCCACAAACGGAGTGGGCTATCAGCCTTACCGCGTGGTTGTCCTGAGCTTTGAGCTGCTGCATGCCCCTGCTACGGTGTGTGGACCTAAGAAGTCCACCAACCTGGTGAAGAACAAGTGTGTGAACTTCAACTTCAACGGCCTGACCGGCACCGGGGTGCTGACAGAGTCTAACAAGAAATTCCTGCCATTCCAGCAATTCGGCCGGGACATCGCCGACACCACCGACGCCGTGCGGGATCCTCAGACCCTCGAAATCCTGGACATCACCCCCTGTAGCTTCGGCGGCGTGAGCGTGATCACCCCTGGCACAAACACCAGCAATCAAGTGGCTGTCCTGTACCAGGATGTCAATTGCACAGAAGTGCCTGTGGCCATCCACGCCGATCAGCTGACCCCCACCTGGCGGGTGTACTCGACAGGAAGCAACGTGTTTCAAACAAGAGCCGGCTGCCTGATCGGGGCCGAGCACGTGAACAATTCCTACGAGTGCGACATCCCCATCGGCGCCGGCATCTGTGCCTCTTACCAGACACAGACCAATTCCCCTCGTAGAGCCAGATCCGTGGCCAGCCAGAGCATCATCGCCTACACCATGAGCCTGGGCGCCGAAAACAGCGTTGCATATTCCAACAACAGCATCGCCATCCCTACCAACTTCACCATCAGCGTGACCACAGAAATCCTGCCTGTGTCCATGACCAAGACAAGCGTTGATTGCACCATGTACATCTGCGGCGATAGCACAGAGTGCAGCAATCTGCTGCTGCAGTACGGTAGCTTCTGCACCCAGCTGAATAGAGCCCTGACCGGCATCGCTGTGGAACAGGACAAAAACACCCAGGAGGTCTTCGCCCAGGTGAAGCAAATCTACAAGACCCCTCCAATCAAGGACTTCGGAGGCTTTAACTTTAGCCAGATCCTGCCTGATCCCTCCAAGCCTAGCAAACGGAGTTTCATCGAGGACCTGCTCTTCAACAAGGTGACCCTGGCTGACGCCGGCTTCATTAAGCAGTACGGCGATTGCCTCGGCGACATCGCTGCAAGAGACCTGATCTGCGCCCAGAAGTTCAACGGCCTGACCGTGCTGCCTCCTCTCCTGACAGACGAGATGATCGCCCAGTACACCTCTGCCCTTCTGGCTGGCACCATCACCAGCGGATGGACCTTTGGAGCCGGAGCCGCCCTGCAGATCCCTTTCGCTATGCAGATGGCCTACAGATTCAACGGGATCGGAGTGACCCAAAACGTGCTGTATGAAAACCAGAAACTGATCGCCAATCAGTTTAACAGCGCCATCGGCAAAATCCAGGATAGCCTGTCCAGCACCGCCAGCGCCCTCGGCAAGCTGCAAGATGTGGTGAATCAAAATGCCCAAGCCCTGAACACACTGGTGAAGCAGCTGAGCAGCAACTTCGGCGCCATCAGCAGCGTGCTGAACGACATCCTGAGCAGACTGGACAAGGTGGAAGCCGAGGTGCAGATCGACAGACTGATCACAGGCAGACTGCAGTCCCTGCAGACCTACGTGACCCAGCAGTTGATTAGAGCCGCTGAGATTAGAGCCAGTGCCAACCTGGCTGCCACAAAGATGTCAGAATGCGTGCTGGGCCAGAGCAAGAGAGTGGACTTCTGCGGCAAAGGCTACCACCTGATGAGCTTTCCTCAGTCTGCACCCCACGGCGTGGTGTTTCTCCACGTGACATACGTGCCCGCGCAAGAAAAGAACTTTACAACCGCCCCAGCGATCTGCCACGACGGCAAGGCCCACTTCCCTCGGGAGGGTGTGTTCGTGAGCAATGGAACACACTGGTTCGTCACCCAGCGGAACTTCTACGAGCCTCAGATCATTACCACCGACAACACCTTCGTGAGCGGCAACTGTGACGTCGTTATCGGCATCGTGAACAATACCGTGTACGACCCCCTGCAGCCTGAGCTGGATAGCTTCAAAGAGGAACTGGACAAGTACTTCAAGAACCACACAAGCCCCGACGTGGACCTAGGCGACATCTCTGGAATCAACGCCAGCGTGGTGAACATCCAAAAGGAAATCGACAGACTGAACGAGGTGGCCAAGAATCTGAATGAAAGCCTGATCGATCTGCAGGAGCTGGGCAAGTACGAGCAGTACATCAAATGGCCTTGGTACATCTGGCTGGGCTTCATCGCTGGTCTGATCGCTATCGTGATGGTGACCATTATGCTGTGCTGCATGACCTCCTGCTGCTCTTGCCTGAAGGGCTGTTGTTCTTGCGGCTCTTGCTGCAAGTTCGACGAGGATGACTCTGAACCTGTTCTGAAGGGCGTGAAGCTGCACTACACCTGATaaacgcgtACCCAAGGTCCAACTCTCCAAGCGGCAATCCTCTCTCGCTTCCTCAGCCCCACTGAATGGTCGCGTAACCGTAATTAATCTAGCTACATTTAAGATTAAGAAAAAATACGGGTAGAATTGGAGTGCCCCAATTGTGCCAAGATGGACTCATCTAGGACAATTGGGCTGTACTTTGATTCTGCCCATTCTTCTAGCAACCTGTTAGCATTTCCGATCGTCCTACAAGGCACAGGAGATGGGAAGAAGCAAATCGCCCCGCAATATAGGATCCAGCGCCTTGACTTGTGGACTGATAGTAAGGAGGACTCAGTATTCATCACCACCTATGGATTCATCTTTCAAGTTGGGAATGAAGAAGCCACTGTCGGCATGATCGATGATAAACCCAAGCGCGAGTTACTTTCCGCTGCGATGCTCTGCCTAGGAAGCGTCCCAAATACCGGAGACCTTATTGAGCTGGCAAGGGCCTGTCTCACTATGATAGTCACATGCAAGAAGAGTGCAACTAATACTGAGAGAATGGTTTTCTCAGTAGTGCAGGCACCCCAAGTGCTGCAAAGCTGTAGGGTTGTGGCAAACAAATACTCATCAGTGAATGCAGTCAAGCACGTGAAAGCGCCAGAGAAGATTCCCGGGAGTGGAACCCTAGAATACAAGGTGAACTTTGTCTCCTTGACTGTGGTACCGAAGAAGGATGTCTACAAGATCCCAGCTGCAGTATTGAAGGTTTCTGGCTCGAGTCTGTACAATCTTGCGCTCAATGTCACTATTAATGTGGAGGTAGACCCGAGGAGTCCTTTGGTTAAATCTTTGTCTAAGTCTGACAGCGGATACTATGCTAACCTCTTCTTGCATATTGGACTTATGACCACCGTAGATAGGAAGGGGAAGAAAGTGACATTTGACAAGCTGGAAAAGAAAATAAGGAGCCTTGATCTATCTGTCGGGCTCAGTGATGTGCTCGGGCCTTCCGTGTTGGTAAAAGCAAGAGGTGCACGGACTAAGCTTTTGGCACCTTTCTTCTCTAGCAGTGGGACAGCCTGCTATCCCATAGCAAATGCTTCTCCTCAGGTGGCCAAGATACTCTGGAGTCAAACCGCGTGCCTGCGGAGCGTTAAAATCATTATCCAAGCAGGTACCCAACGCGCTGTCGCAGTGACCGCCGACCACGAGGTTACCTCTACTAAGCTGGAGAAGGGGCACACCCTTGCCAAATACAATCCTTTTAAGAAATAAGCTGCGTCTCTGAGATTGCGCTCCGCCCACTCACCCAGATCATCATGACACAAAAAACTAATCTGTCTTGATTATTTACAGTTAGTTTACCTGTCTATCAAGTTAGAAAAAACACGGGTAGAAGATTCTGGATCCCGGTTGGCGCCCTCCAGGTGCAAGttaattaaATGGGCTCCAGACCTTCTACCAAGAACCCAGCACCTATGATGCTGACTATCCGGGTTGCGCTGGTACTGAGTTGCATCTGTCCGGCAAACTCCATTGATGGCAGGCCTCTTGCAGCTGCAGGAATTGTGGTTACAGGAGACAAAGCCGTCAACATATACACCTCATCCCAGACAGGATCAATCATAGTTAAGCTCCTCCCGAATCTGCCCAAGGATAAGGAGGCATGTGCGAAAGCCCCCTTGGATGCATACAACAGGACATTGACCACTTTGCTCACCCCCCTTGGTGACTCTATCCGTAGGATACAAGAGTCTGTGACTACATCTGGAGGGGGGAGACAGGGGCGCCTTATAGGCGCCATTATTGGCGGTGTGGCTCTTGGGGTTGCAACTGCCGCACAAATAACAGCGGCCGCAGCTCTGATACAAGCCAAACAAAATGCTGCCAACATCCTCCGACTTAAAGAGAGCATTGCCGCAACCAATGAGGCTGTGCATGAGGTCACTGACGGATTATCGCAACTAGCAGTGGCAGTTGGGAAGATGCAGCAGTTTGTTAATGACCAATTTAATAAAACAGCTCAGGAATTAGACTGCATCAAAATTGCACAGCAAGTTGGTGTAGAGCTCAACCTGTACCTAACCGAATTGACTACAGTATTCGGACCACAAATCACTTCACCTGCTTTAAACAAGCTGACTATTCAGGCACTTTACAATCTAGCTGGTGGAAATATGGATTACTTATTGACTAAGTTAGGTGTAGGGAACAATCAACTCAGCTCATTAATCGGTAGCGGCTTAATCACtGGcAACCCTATTCTATACGACTCACAGACTCAACTCTTGGGTATACAGGTAACTgcaCCTTCAGTCGGGAACCTAAATAATATGCGTGCCACCTACTTGGAAACCTTATCCGTAAGCACAACCAGGGGATTTGCCTCGGCACTTGTCCCCAAAGTGGTGACACAGGTCGGTTCTGTGATAGAAGAACTTGACACCTCATACTGTATAGAAACTGACTTAGATTTATATTGTACAAGAATAGTAACGTTCCCTATGTCCCCTGGTATTTATTCCTGCTTGAGCGGCAATACGTCGGCCTGTATGTACTCAAAGACCGAAGGCGCACTTACTACACCATACATGACTATCAAAGGTTCAGTCATCGCCAACTGCAAGATGACAACATGTAGATGTGTAAACCCCCCGGGTATCATATCGCAAAACTATGGAGAAGCCGTGTCTCTAATAGATAAACAATCATGCAATGTTTTATCCTTAGGCGGGATAACTTTAAGGCTCAGTGGGGAATTCGATGTAACTTATCAGAAGAATATCTCAATACAAGATTCTCAAGTAATAATAACAGGCAATCTTGATATCTCAACTGAGCTTGGGAATGTCAACAACTCGATCAGTAATGCTTTGAATAAGTTAGAGGAAAGCAACAGAAAACTAGACAAAGTCAATGTCAAACTGACTAGCACATCTGCTCTCATTACgTATATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTGATTCTAGCATGCTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTTATTATGGCTTGGGAATAATACaCTcGATCAGATGAGAGCCACTACAAAAATGTGAACACAGATGAGGAACGAAGGTTTCCCTAATAGTAATTTGTGTGAAAGTTCTGGTAGTCTGTCAGTTCAGAGAGTTAAGAAAAAACTACCGGTTGTAGATGACCAAAGGACGATATACGGGTAGAACGGTAAGAGAGGCCGCCCCTCAATTGCGAGCCAGGCTTCACAACCTCCGTTCTACCGCTTCACCGACAACAGTCCTCAATCATGGACCGCGCCGTTAGCCAAGTTGCGTTAGAGAATGATGAAAGAGAGGCAAAAAATACATGGCGCTTGATATTCCGGATTGCAATCTTATTCTTAACAGTAGTGACCTTGGCTATATCTGTAGCCTCCCTTTTATATAGCATGGGGGCTAGCACACCTAGCGATCTTGTAGGCATACCGACTAGGATTTCCAGGGCAGAAGAAAAGATTACATCTACACTTGGTTCCAATCAAGATGTAGTAGATAGGATATATAAGCAAGTGGCCCTTGAGTCTCCGTTGGCATTGTTAAATACTGAGACCACAATTATGAACGCAATAACATCTCTCTCTTATCAGATTAATGGAGCTGCAAACAACAGTGGGTGGGGGGCACCTATCCATGACCCAGATTATATAGGGGGGATAGGCAAAGAACTCATTGTAGATGATGCTAGTGATGTCACATCATTCTATCCCTCTGCATTTCAAGAACATCTGAATTTTATCCCGGCGCCTACTACAGGATCAGGTTGCACTCGAATACCCTCATTTGACATGAGTGCTACCCATTACTGCTACACCCATAATGTAATATTGTCTGGATGCAGAGATCACTCACATTCATATCAGTATTTAGCACTTGGTGTGCTCCGGACATCTGCAACAGGGAGGGTATTCTTTTCTACTCTGCGTTCCATCAACCTGGACGACACCCAAAATCGGAAGTCTTGCAGTGTGAGTGCAACTCCCCTGGGTTGTGATATGCTGTGCTCGAAAGTCACGGAGACAGAGGAAGAAGATTATAACTCAGCTGTCCCTACGCGGATGGTACATGGGAGGTTAGGGTTCGACGGCCAGTACCACGAAAAGGACCTAGATGTCACAACATTATTCGGGGACTGGGTGGCCAACTACCCAGGAGTAGGGGGTGGATCTTTTATTGACAGCCGCGTATGGTTCTCAGTCTACGGAGGGTTAAAACCCAATTCACCCAGTGACACTGTACAGGAAGGGAAATATGTGATATACAAGCGATACAATGACACATGCCCAGATGAGCAAGACTACCAGATTCGAATGGCCAAGTCTTCGTATAAGCCTGGACGGTTTGGTGGGAAACGCATACAGCAGGCTATCTTATCTATCAAGGTGTCAACATCCTTAGGCGAAGACCCGGTACTGACTGTACCGCCCAACACAGTCACACTCATGGGGGCCGAAGGCAGAATTCTCACAGTAGGGACATCTCATTTCTTGTATCAACGAGGGTCATCATACTTCTCTCCCGCGTTATTATATCCTATGACAGTCAGCAACAAAACAGCCACTCTTCATAGTCCTTATACATTCAATGCCTTCACTCGGCCAGGTAGTATCCCTTGCCAGGCTTCAGCAAGATGCCCCAACTCGTGTGTTACTGGAGTCTATACAGATCCATATCCCCTAATCTTCTATAGAAACCACACCTTGCGAGGGGTATTCGGGACAATGCTTGATGGTGTACAAGCAAGACTTAACCCTGCGTCTGCAGTATTCGATAGCACATCCCGCAGTCGCATTACTCGAGTGAGTTCAAGCAGTACCAAAGCAGCATACACAACATCAACTTGTTTTAAAGTGGTCAAGACTAATAAGACCTATTGTCTCAGCATTGCTGAAATATCTAATACTCTCTTCGGAGAATTCAGAATCGTCCCGTTACTAGTTGAGATCCTCAAAGATGACGGGGTTAGAGAAGCCAGGTCTGGCTAGggcgcgccTTGAGTCAATTATAAAGGAGTTGGAAAGATGGCATTGTATCACCTATCTTCTGCGACATCAAGAATCAAACCGAATGCCGGCGCGTGCTCGAATTCCATGTTGCCAGTTGACCACAATCAGCCAGTGCTCATGCGATCAGATTAAGCCTTGTCATTAATCTCTTGATTAAGAAAAAATGTAAGTGGCAATGAGATACAAGGCAAAACAGCTCATGGTAAATAATACGGGTAGGACATGGCGAGCTCCGGTCCTGAAAGGGCAGAGCATCAGATTATCCTACCAGAGCCACACCTGTCTTCACCATTGGTCAAGCACAAACTACTCTATTACTGGAAATTAACTGGGCTACCGCTTCCTGATGAATGTGACTTCGACCACCTCATTCTCAGCCGACAATGGAAAAAAATACTTGAATCGGCCTCTCCTGATACTGAGAGAATGATAAAACTCGGAAGGGCAGTACACCAAACTCTTAACCACAATTCCAGAATAACCGGAGTGCTCCACCCCAGGTGTTTAGAACAACTGGCTAATATTGAGGTCCCAGATTCAACCAACAAATTTCGGAAGATTGAGAAGAAGATCCAAATTCACAACACGAGATATGGAGAACTGTTCACAAGGCTGTGTACGCATATAGAGAAGAAACTGCTGGGGTCATCTTGGTCTAACAATGTCCCCCGGTCAGAGGAGTTCAGCAGCATTCGTACGGATCCGGCATTCTGGTTTCACTCAAAATGGTCCACAGCCAAGTTTGCATGGCTCCATATAAAACAGATCCAGAGGCATCTGATGGTGGCAGCTAAGACAAGGTCTGCGGCCAACAAATTGGTGATGCTAACCCATAAGGTAGGCCAAGTCTTTGTCACTCCTGAACTTGTCGTTGTGACGCATACGAATGAGAACAAGTTCACATGTCTTACCCAGGAACTTGTATTGATGTATGCAGATATGATGGAGGGCAGAGATATGGTCAACATAATATCAACCACGGCGGTGCATCTCAGAAGCTTATCAGAGAAAATTGATGACATTTTGCGGTTAATAGACGCTCTGGCAAAAGACTTGGGTAATCAAGTCTACGATGTTGTATCACTAATGGAGGGATTTGCATACGGAGCTGTCCAGCTACTCGAGCCGTCAGGTACATTTGCAGGAGATTTCTTCGCATTCAACCTGCAGGAGCTTAAAGACATTCTAATTGGCCTCCTCCCCAATGATATAGCAGAATCCGTGACTCATGCAATCGCTACTGTATTCTCTGGTTTAGAACAGAATCAAGCAGCTGAGATGTTGTGTCTGTTGCGTCTGTGGGGTCACCCACTGCTTGAGTCCCGTATTGCAGCAAAGGCAGTCAGGAGCCAAATGTGCGCACCGAAAATGGTAGACTTTGATATGATCCTTCAGGTACTGTCTTTCTTCAAGGGAACAATCATCAACGGGTACAGAAAGAAGAATGCAGGTGTGTGGCCGCGAGTCAAAGTGGATACAATATATGGGAAGGTCATTGGGCAACTACATGCAGATTCAGCAGAGATTTCACACGATATCATGTTGAGAGAGTATAAGAGTTTATCTGCACTTGAATTTGAGCCATGTATAGAATATGACCCTGTCACCAACCTGAGCATGTTCCTAAAAGACAAGGCAATCGCACACCCCAACGATAATTGGCTTGCCTCGTTTAGGCGGAACCTTCTCTCCGAAGACCAGAAGAAACATGTAAAAGAAGCAACTTCGACTAATCGCCTCTTGATAGAGTTTTTAGAGTCAAATGATTTTGATCCATATAAAGAGATGGAATATCTGACGACCCTTGAGTACCTTAGAGATGACAATGTGGCAGTATCATACTCGCTCAAGGAGAAGGAAGTGAAAGTTAATGGACGGATCTTCGCTAAGCTGACAAAGAAGTTAAGGAACTGTCAGGTGATGGCGGAAGGGATCCTAGCCGATCAGATTGCACCTTTCTTTCAGGGAAATGGAGTCATTCAGGATAGCATATCCTTGACCAAGAGTATGCTAGCGATGAGTCAACTGTCTTTTAACAGCAATAAGAAACGTATCACTGACTGTAAAGAAAGAGTATCTTCAAACCGCAATCATGATCCGAAAAGCAAGAACCGTCGGAGAGTTGCAACCTTCATAACAACTGACCTGCAAAAGTACTGTCTTAATTGGAGATATCAGACAATCAAATTGTTCGCTCATGCCATCAATCAGTTGATGGGCCTACCTCACTTCTTCGAATGGATTCACCTAAGACTGATGGACACTACGATGTTCGTAGGAGACCCTTTCAATCCTCCAAGTGACCCTACTGACTGTGACCTCTCAAGAGTCCCTAATGATGACATATATATTGTCAGTGCCAGAGGGGGTATCGAAGGATTATGCCAGAAGCTATGGACAATGATCTCAATTGCTGCAATCCAACTTGCTGCAGCTAGATCGCATTGTCGTGTTGCCTGTATGGTACAGGGTGATAATCAAGTAATAGCAGTAACGAGAGAGGTAAGATCAGACGACTCTCCGGAGATGGTGTTGACACAGTTGCATCAAGCCAGTGATAATTTCTTCAAGGAATTAATTCATGTCAATCATTTGATTGGCCATAATTTGAAGGATCGTGAAACCATCAGGTCAGACACATTCTTCATATACAGCAAACGAATCTTCAAAGATGGAGCAATCCTCAGTCAAGTCCTCAAAAATTCATCTAAATTAGTGCTAGTGTCAGGTGATCTCAGTGAAAACACCGTAATGTCCTGTGCCAACATTGCCTCTACTGTAGCACGGCTATGCGAGAACGGGCTTCCCAAAGACTTCTGTTACTATTTAAACTATATAATGAGTTGTGTGCAGACATACTTTGACTCTGAGTTCTCCATCACCAACAATTCGCACCCCGATCTTAATCAGTCGTGGATTGAGGACATCTCTTTTGTGCACTCATATGTTCTGACTCCTGCCCAATTAGGGGGACTGAGTAACCTTCAATACTCAAGGCTCTACACTAGAAATATCGGTGACCCGGGGACTACTGCTTTTGCAGAGATCAAGCGACTAGAAGCAGTGGGATTACTGAGTCCTAACATTATGACTAATATCTTAACTAGGCCGCCTGGGAATGGAGATTGGGCCAGTCTGTGCAACGACCCATACTCTTTCAATTTTGAGACTGTTGCAAGCCCAAATATTGTTCTTAAGAAACATACGCAAAGAGTCCTATTTGAAACTTGTTCAAATCCCTTATTGTCTGGAGTGCACACAGAGGATAATGAGGCAGAAGAGAAGGCATTGGCTGAATTCTTGCTTAATCAAGAGGTGATTCATCCCCGCGTTGCGCATGCCATCATGGAGGCAAGCTCTGTAGGTAGGAGAAAGCAAATTCAAGGGCTTGTTGACACAACAAACACCGTAATTAAGATTGCGCTTACTAGGAGGCCATTAGGCATCAAGAGGCTGATGCGGATAGTCAATTATTCTAGCATGCATGCAATGCTGTTTAGAGACGATGTTTTTTCCTCCAGTAGATCCAACCACCCCTTAGTCTCTTCTAATATGTGTTCTCTGACACTGGCAGACTATGCACGGAATAGAAGCTGGTCACCTTTGACGGGAGGCAGGAAAATACTGGGTGTATCTAATCCTGATACGATAGAACTCGTAGAGGGTGAGATTCTTAGTGTAAGCGGAGGGTGTACAAGATGTGACAGCGGAGATGAACAATTTACTTGGTTCCATCTTCCAAGCAATATAGAATTGACCGATGACACCAGCAAGAATCCTCCGATGAGGGTACCATATCTCGGGTCAAAGACACAGGAGAGGAGAGCTGCCTCACTTGCAAAAATAGCTCATATGTCGCCACATGTAAAGGCTGCCCTAAGGGCATCATCCGTGTTGATCTGGGCTTATGGGGATAATGAAGTAAATTGGACTGCTGCTCTTACGATTGCAAAATCTCGGTGTAATGTAAACTTAGAGTATCTTCGGTTACTGTCCCCTTTACCCACGGCTGGGAATCTTCAACATAGACTAGATGATGGTATAACTCAGATGACATTCACCCCTGCATCTCTCTACAGGgtgtcaccttacattcacatatccaatgattctcaaaggctgttcactgaagaaggagtcaaagaggggaatgtggtttaccaacagatcATGCTCTTGGGTTTATCTCTAATCGAATCGATCTTTCCAATGACAACAACCAGGACATATGATGAGATCACACTGCACCTAGATAGTAAATTTAGTTGCTGTATCAGAGAAGCACCTGTTGCGGTTCCTTTCGAGCTACTTGGGGTGGTACCGGAACTGAGGACAGTGACCTCAAATAAGTTTATGTATGATCCTAGCCCTGTATCGGAGGGAGACTTTGCGAGACTTGACTTAGCTATCTTCAAGAGTTATGAGCTTAATCTGGAGTCATATCCCACGATAGAGCTAATGAACATTCTTTCAATATCCAGCGGGAAGTTGATTGGCCAGTCTGTGGTTTCTTATGATGAAGATACCTCCATAAAGAATGACGCCATAATAGTGTATGACAATACCCGAAATTGGATCAGTGAAGCTCAGAATTCAGATGTGGTCCGCCTATTTGAATATGCAGCACTTGAAGTGCTCCTCGACTGTTCTTACCAACTCTATTACCTGAGAGTAAGAGGCCTAGACAATATTGTCTTATATATGGGTGATTTATACAAGAATATGCCAGGAATTCTACTTTCCAACATTGCAGCTACAATATCTCATCCCGTCATTCATTCAAGGTTACATGCAGTGGGCCTGGTCAACCATGACGGATCACACCAACTTGCAGATACGGATTTTATCGAAATGTCTGCAAAACTATTAGTATCTTGCACCCGACGTGTGATCTCCGGCTTATATTCAGGAAATAAGTATGATCTGCTGTTCCCATCTGTCTTAGATGATAACCTGAATGAGAAGATGCTTCAGCTGATATCCCGGTTATGCTGTCTGTACACGGTACTCTTTGCTACAACAAGAGAAATCCCGAAAATAAGAGGCTTAACTGCAGAAGAGAAATGTTCAATACTCACTGAGTATTTACTGTCGGATGCTGTGAAACCATTACTTAGCCCCGATCAAGTGAGCTCTATCATGTCTCCTAACATAATTACATTCCCAGCTAATCTGTACTACATGTCTCGGAAGAGCCTCAATTTGATCAGGGAAAGGGAGGACAGGGATACTATCCTGGCGTTGTTGTTCCCCCAAGAGCCATTATTAGAGTTCCCTTCTGTGCAAGATATTGGTGCTCGAGTGAAAGATCCATTCACCCGACAACCTGCGGCATTTTTGCAAGAGTTAGATTTGAGTGCTCCAGCAAGGTATGACGCATTCACACTTAGTCAGATTCATCCTGAACTCACATCTCCAAATCCGGAGGAAGACTACTTAGTACGATACTTGTTCAGAGGGATAGGGACTGCATCTTCCTCTTGGTATAAGGCATCTCATCTCCTTTCTGTACCCGAGGTAAGATGTGCAAGACACGGGAACTCCTTATACTTAGCTGAAGGGAGCGGAGCCATCATGAGTCTTCTCGAACTGCATGTACCACATGAAACTATCTATTACAATACGCTCTTTTCAAATGAGATGAACCCCCCGCAACGACATTTCGGGCCGACCCCAACTCAGTTTTTGAATTCGGTTGTTTATAGGAATCTACAGGCGGAGGTAACATGCAAAGATGGATTTGTCCAAGAGTTCCGTCCATTATGGAGAGAAAATACAGAGGAAAGTGACCTGACCTCAGATAAAGCAGTGGGGTATATTACATCTGCAGTGCCCTACAGATCTGTATCATTGCTGCATTGTGACATTGAAATTCCTCCAGGGTCCAATCAAAGCTTACTAGATCAACTAGCTATCAATTTATCTCTGATTGCCATGCATTCTGTAAGGGAGGGCGGGGTAGTAATCATCAAAGTGTTGTATGCAATGGGATACTACTTTCATCTACTCATGAACTTGTTTGCTCCGTGTTCCACAAAAGGATATATTCTCTCTAATGGTTATGCATGTCGAGGAGATATGGAGTGTTACCTGGTATTTGTCATGGGTTACCTGGGCGGGCCTACATTTGTACATGAGGTGGTGAGGATGGCAAAAACTCTGGTGCAGCGGCACGGTACGCTCTTGTCTAAATCAGATGAGATCACACTGACCAGGTTATTCACCTCACAGCGGCAGCGTGTGACAGACATCCTATCCAGTCCTTTACCAAGATTAATAAAGTACTTGAGGAAGAATATTGACACTGCGCTGATTGAAGCCGGGGGACAGCCCGTCCGTCCATTCTGTGCGGAGAGTCTGGTGAGCACGCTAGCGAACATAACTCAGATAACCCAGATTATCGCTAGTCACATTGACACAGTTATCCGGTCTGTGATATATATGGAAGCTGAGGGTGATCTCGCTGACACAGTATTTCTATTTACCCCTTACAATCTCTCTACTGACGGGAAAAAGAGGACATCACTTATACAGTGCACGAGACAGATCCTAGAGGTTACAATACTAGGTCTTAGAGTCGAAAATCTCAATAAAATAGGCGATATAATCAGCCTAGTGCTTAAAGGCATGATCTCCATGGAGGACCTTATCCCACTAAGGACATACTTGAAGCATAGTACCTGCCCTAAATATTTGAAGGCTGTCCTAGGTATTACCAAACTCAAAGAAATGTTTACAGACACTTCTGTATTGTACTTGACTCGTGCTCAACAAAAATTCTACATGAAAACTATAGGCAATGCAGTCAAAGGATATTACAGTAACTGTGACTCTTAACGAAAATCACATATTAATAGGCTCCTTTTTTGGCCAATTGTATTCTTGTTGATTTAATCATATTATGTTAGAAAAAAGTTGAACCCTGACTCCTTAGGACTCGAATTCGAACTCAAATAAATGTCTTAAAAAAAGGTTGCGCACAATTATTCTTGAGTGTAGTCTCGTCATTCACCAAATCTTTGTTTGGTGGCCGGCATGGTCCCAGCCTCCTCGCTGGCGCCGGCTGGGCAACATTCCGAGGGGACCGTCCCCTCGGTAATGGCGAATGGGACGTCGACTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTATA SEQ ID NO:TAATACGACTCACTATAGGGACCAAACAGAGAATCCGTGAGTTACGATAAAAGGCGAAGG3; nucleotideAGCAATTGAAGTCGCACGGGTAGAAGGTGTGAATCTCGAGTGCGAGCCCGAAGCACAAAC sequence ofTCGAGAAAGCCTTCTGCCAACATGTCTTCCGTATTTGATGAGTACGAACAGCTCCTCGCG NDV-Δ19-SGCTCAGACTCGCCCCAATGGAGCTCATGGAGGGGGAGAAAAAGGGAGTACCTTAAAAGTA MolecularGACGTCCCGGTATTCACTCTTAACAGTGATGACCCAGAAGATAGATGGAGCTTTGTGGTA CloneTTCTGCCTCCGGATTGCTGTTAGCGAAGATGCCAACAAACCACTCAGGCAAGGTGCTCTC AF077761.1_ATATCTCTTTTATGCTCCCACTCACAGGTAATGAGGAACCATGTTGCCATTGCAGGGAAA LaSota_KanCAGAATGAAGCCACATTGGCCGTGCTTGAGATTGATGGCTTTGCCAACGGCACGCCCCAG R (withTTCAACAATAGGAGTGGAGTGTCTGAAGAGAGAGCACAGAGATTTGCGATGATAGCAGGA stabilizingTCTCTCCCTCGGGCATGCAGCAACGGAACCCCGTTCGTCACAGCCGGGGCAGAAGATGAT sequence inGCACCAGAAGACATCACCGATACCCTGGAGAGGATCCTCTCTATCCAGGCTCAAGTATGG L)GTCACAGTAGCAAAAGCCATGACTGCGTATGAGACTGCAGATGAGTCGGAAACAAGGCGAATCAATAAGTATATGCAGCAAGGCAGGGTCCAAAAGAAATACATCCTCTACCCCGTATGCAGGAGCACAATCCAACTCACGATCAGACAGTCTCTTGCAGTCCGCATCTTTTTGGTTAGCGAGCTCAAGAGAGGCCGCAACACGGCAGGTGGTACCTCTACTTATTATAACCTGGTAGGGGACGTAGACTCATACATCAGGAATACCGGGCTTACTGCATTCTTCTTGACACTCAAGTACGGAATCAACACCAAGACATCAGCCCTTGCACTTAGTAGCCTCTCAGGCGACATCCAGAAGATGAAGCAGCTCATGCGTTTGTATCGGATGAAAGGAGATAATGCGCCGTACATGACATTACTTGGTGATAGTGACCAGATGAGCTTTGCGCCTGCCGAGTATGCACAACTTTACTCCTTTGCCATGGGTATGGCATCAGTCCTAGATAAAGGTACTGGGAAATACCAATTTGCCAGGGACTTTATGAGCACATCATTCTGGAGACTTGGAGTAGAGTACGCTCAGGCTCAGGGAAGTAGCATTAACGAGGATATGGCTGCCGAGCTAAAGCTAACCCCAGCAGCAATGAAGGGCCTGGCAGCTGCTGCCCAACGGGTCTCCGACGATACCAGCAGCATATACATGCCTACTCAACAAGTCGGAGTCCTCACTGGGCTTAGCGAGGGGGGGTCCCAAGCTCTACAAGGCGGATCGAATAGATCGCAAGGGCAACCAGAAGCCGGGGATGGGGAGACCCAATTCCTGGATCTGATGAGAGCGGTAGCAAATAGCATGAGGGAGGCGCCAAACTCTGCACAGGGCACTCCCCAATCGGGGCCTCCCCCAACTCCTGGGCCATCCCAAGATAACGACACCGACTGGGGGTATTGATGGACAAAACCCAGCCTGCTTCCACAAAAACATCCCAATGCCCTCACCCGTAGTCGACCCCTCGATTTGCGGCTCTATATGACCACACCCTCAAACAAACATCCCCCTCTTTCCTCCCTCCCCCTGCTGTACAACTCCGCACGCCCTAGATACCACAGGCACAATGCGGCTCACTAACAATCAAAACAGAGCCGAGGGAATTAGAAAAAAGTACGGGTAGAAGAGGGATATTCAGAGATCAGGGCAAGTCTCCCGAGTCTCTGCTCTCTCCTCTACCTGATAGACCAGGACAAACATGGCCACCTTTACAGATGCAGAGATCGACGAGCTATTTGAGACAAGTGGAACTGTCATTGACAACATAATTACAGCCCAGGGTAAACCAGCAGAGACTGTTGGAAGGAGTGCAATCCCACAAGGCAAGACCAAGGTGCTGAGCGCAGCATGGGAGAAGCATGGGAGCATCCAGCCACCGGCCAGTCAAGACAACCCCGATCGACAGGACAGATCTGACAAACAACCATCCACACCCGAGCAAACGACCCCGCATGACAGCCCGCCGGCCACATCCGCCGACCAGCCCCCCACCCAGGCCACAGACGAAGCCGTCGACACACAGTTCAGGACCGGAGCAAGCAACTCTCTGCTGTTGATGCTTGACAAGCTCAGCAATAAATCGTCCAATGCTAAAAAGGGCCCATGGTCGAGCCCCCAAGAGGGGAATCACCAACGTCCGACTCAACAGCAGGGGAGTCAACCCAGTCGCGGAAACAGTCAGGAAAGACCGCAGAACCAAGTCAAGGCCGCCCCTGGAAACCAGGGCACAGACGTGAACACAGCATATCATGGACAATGGGAGGAGTCACAACTATCAGCTGGTGCAACCCCTCATGCTCTCCGATCAAGGCAGAGCCAAGACAATACCCTTGTATCTGCGGATCATGTCCAGCCACCTGTAGACTTTGTGCAAGCGATGATGTCTATGATGGAGGCGATATCACAGAGAGTAAGTAAGGTTGACTATCAGCTAGATCTTGTCTTGAAACAGACATCCTCCATCCCTATGATGCGGTCCGAAATCCAACAGCTGAAAACATCTGTTGCAGTCATGGAAGCCAACTTGGGAATGATGAAGATTCTGGATCCCGGTTGTGCCAACATTTCATCTCTGAGTGATCTACGGGCAGTTGCCCGATCTCACCCGGTTTTAGTTTCAGGCCCTGGAGACCCCTCTCCCTATGTGACACAAGGAGGCGAAATGGCACTTAATAAACTTTCGCAACCAGTGCCACATCCATCTGAATTGATTAAACCCGCCACTGCATGCGGGCCTGATATAGGAGTGGAAAAGGACACTGTCCGTGCATTGATCATGTCACGCCCAATGCACCCGAGTTCTTCAGCCAAGCTCCTAAGCAAGTTAGATGCAGCCGGGTCGATCGAGGAAATCAGGAAAATCAAGCGCCTTGCTCTAAATGGCTAATTACTACTGCCACACGTAGCGGGTCCCTGTCCACTCGGCATCACACGGAATCTGCACCGAGTTCCCCCtctagaTTAGAAAAAATACGGGTAGAACCGCCACCATGTTCGTGTTCCTGGTCCTGCTGCCACTGGTAAGCTCCCAATGTGTAAACTTAACCACAAGAACCCAGCTCCCACCTGCCTACACCAACAGCTTCACCAGAGGCGTTTATTACCCCGACAAGGTATTCCGGTCTTCTGTTCTGCACTCTACCCAGGACCTGTTTCTGCCCTTTTTCAGCAACGTGACATGGTTCCACGCCATCCACGTGTCTGGCACAAACGGCACCAAGCGGTTTGATAATCCTGTGCTCCCTTTCAATGACGGCGTGTACTTCGCCTCTACTGAGAAGAGCAACATCATCCGGGGCTGGATCTTTGGCACAACACTGGACTCTAAAACCCAGAGCCTGCTGATCGTGAACAACGCCACCAACGTGGTGATTAAGGTGTGCGAGTTCCAGTTCTGCAATGACCCTTTCCTCGGCGTGTACTACCACAAGAACAACAAAAGTTGGATGGAAAGCGAATTCAGGGTGTACTCAAGCGCCAACAACTGTACCTTCGAGTACGTGAGCCAGCCTTTCCTGATGGACCTAGAAGGTAAGCAGGGCAATTTCAAGAACCTCAGAGAGTTCGTGTTCAAGAATATTGACGGCTACTTCAAAATCTACAGCAAGCACACCCCAATCAACCTGGTGCGGGACCTGCCCCAGGGCTTTAGCGCGCTGGAGCCTCTGGTGGACCTGCCTATCGGCATCAACATCACCCGGTTCCAGACACTGCTGGCTCTGCATAGAAGCTACCTGACACCTGGCGACAGTTCTTCTGGCTGGACAGCCGGCGCCGCCGCCTACTACGTGGGCTACCTGCAGCCTAGAACATTCCTGCTGAAATACAACGAGAACGGCACGATCACAGACGCCGTGGACTGCGCCCTGGATCCCCTGTCTGAGACAAAGTGCACCCTGAAGTCTTTCACCGTGGAGAAGGGCATCTACCAGACCTCCAACTTCAGAGTGCAGCCTACCGAATCCATCGTGCGCTTTCCCAACATCACCAACCTGTGCCCCTTCGGCGAGGTCTTTAATGCCACGAGATTCGCCAGCGTGTATGCCTGGAACAGAAAGAGAATCAGCAACTGCGTGGCCGACTACAGCGTGCTGTACAACAGCGCCTCTTTCAGCACATTTAAGTGCTACGGAGTGTCTCCTACCAAACTCAACGATCTGTGCTTCACGAACGTGTATGCCGACAGCTTCGTGATCCGAGGAGATGAGGTGCGGCAGATCGCTCCAGGACAGACAGGCAAGATCGCCGACTACAACTACAAGCTGCCCGACGACTTTACCGGCTGCGTGATCGCTTGGAACAGCAATAACCTGGACTCAAAGGTTGGAGGAAACTACAACTACCTGTACAGACTGTTCAGAAAGTCCAACCTGAAGCCCTTCGAGAGAGACATCTCTACAGAAATCTACCAGGCCGGCAGCACCCCATGTAACGGCGTGGAAGGCTTCAACTGCTACTTCCCTCTGCAGTCTTATGGCTTCCAGCCCACAAACGGAGTGGGCTATCAGCCTTACCGCGTGGTTGTCCTGAGCTTTGAGCTGCTGCATGCCCCTGCTACGGTGTGTGGACCTAAGAAGTCCACCAACCTGGTGAAGAACAAGTGTGTGAACTTCAACTTCAACGGCCTGACCGGCACCGGGGTGCTGACAGAGTCTAACAAGAAATTCCTGCCATTCCAGCAATTCGGCCGGGACATCGCCGACACCACCGACGCCGTGCGGGATCCTCAGACCCTCGAAATCCTGGACATCACCCCCTGTAGCTTCGGCGGCGTGAGCGTGATCACCCCTGGCACAAACACCAGCAATCAAGTGGCTGTCCTGTACCAGGATGTCAATTGCACAGAAGTGCCTGTGGCCATCCACGCCGATCAGCTGACCCCCACCTGGCGGGTGTACTCGACAGGAAGCAACGTGTTTCAAACAAGAGCCGGCTGCCTGATCGGGGCCGAGCACGTGAACAATTCCTACGAGTGCGACATCCCCATCGGCGCCGGCATCTGTGCCTCTTACCAGACACAGACCAATTCCCCTCGTAGAGCCAGATCCGTGGCCAGCCAGAGCATCATCGCCTACACCATGAGCCTGGGCGCCGAAAACAGCGTTGCATATTCCAACAACAGCATCGCCATCCCTACCAACTTCACCATCAGCGTGACCACAGAAATCCTGCCTGTGTCCATGACCAAGACAAGCGTTGATTGCACCATGTACATCTGCGGCGATAGCACAGAGTGCAGCAATCTGCTGCTGCAGTACGGTAGCTTCTGCACCCAGCTGAATAGAGCCCTGACCGGCATCGCTGTGGAACAGGACAAAAACACCCAGGAGGTCTTCGCCCAGGTGAAGCAAATCTACAAGACCCCTCCAATCAAGGACTTCGGAGGCTTTAACTTTAGCCAGATCCTGCCTGATCCCTCCAAGCCTAGCAAACGGAGTTTCATCGAGGACCTGCTCTTCAACAAGGTGACCCTGGCTGACGCCGGCTTCATTAAGCAGTACGGCGATTGCCTCGGCGACATCGCTGCAAGAGACCTGATCTGCGCCCAGAAGTTCAACGGCCTGACCGTGCTGCCTCCTCTCCTGACAGACGAGATGATCGCCCAGTACACCTCTGCCCTTCTGGCTGGCACCATCACCAGCGGATGGACCTTTGGAGCCGGAGCCGCCCTGCAGATCCCTTTCGCTATGCAGATGGCCTACAGATTCAACGGGATCGGAGTGACCCAAAACGTGCTGTATGAAAACCAGAAACTGATCGCCAATCAGTTTAACAGCGCCATCGGCAAAATCCAGGATAGCCTGTCCAGCACCGCCAGCGCCCTCGGCAAGCTGCAAGATGTGGTGAATCAAAATGCCCAAGCCCTGAACACACTGGTGAAGCAGCTGAGCAGCAACTTCGGCGCCATCAGCAGCGTGCTGAACGACATCCTGAGCAGACTGGACAAGGTGGAAGCCGAGGTGCAGATCGACAGACTGATCACAGGCAGACTGCAGTCCCTGCAGACCTACGTGACCCAGCAGTTGATTAGAGCCGCTGAGATTAGAGCCAGTGCCAACCTGGCTGCCACAAAGATGTCAGAATGCGTGCTGGGCCAGAGCAAGAGAGTGGACTTCTGCGGCAAAGGCTACCACCTGATGAGCTTTCCTCAGTCTGCACCCCACGGCGTGGTGTTTCTCCACGTGACATACGTGCCCGCGCAAGAAAAGAACTTTACAACCGCCCCAGCGATCTGCCACGACGGCAAGGCCCACTTCCCTCGGGAGGGTGTGTTCGTGAGCAATGGAACACACTGGTTCGTCACCCAGCGGAACTTCTACGAGCCTCAGATCATTACCACCGACAACACCTTCGTGAGCGGCAACTGTGACGTCGTTATCGGCATCGTGAACAATACCGTGTACGACCCCCTGCAGCCTGAGCTGGATAGCTTCAAAGAGGAACTGGACAAGTACTTCAAGAACCACACAAGCCCCGACGTGGACCTAGGCGACATCTCTGGAATCAACGCCAGCGTGGTGAACATCCAAAAGGAAATCGACAGACTGAACGAGGTGGCCAAGAATCTGAATGAAAGCCTGATCGATCTGCAGGAGCTGGGCAAGTACGAGCAGTACATCAAATGGCCTTGGTACATCTGGCTGGGCTTCATCGCTGGTCTGATCGCTATCGTGATGGTGACCATTATGCTGTGCTGCATGACCTCCTGCTGCTCTTGCCTGAAGGGCTGTTGTTCTTGCGGCTCTTGCTGCTGATGATaaacgcgtACCCAAGGTCCAACTCTCCAAGCGGCAATCCTCTCTCGCTTCCTCAGCCCCACTGAATGGTCGCGTAACCGTAATTAATCTAGCTACATTTAAGATTAAGAAAAAATACGGGTAGAATTGGAGTGCCCCAATTGTGCCAAGATGGACTCATCTAGGACAATTGGGCTGTACTTTGATTCTGCCCATTCTTCTAGCAACCTGTTAGCATTTCCGATCGTCCTACAAGGCACAGGAGATGGGAAGAAGCAAATCGCCCCGCAATATAGGATCCAGCGCCTTGACTTGTGGACTGATAGTAAGGAGGACTCAGTATTCATCACCACCTATGGATTCATCTTTCAAGTTGGGAATGAAGAAGCCACTGTCGGCATGATCGATGATAAACCCAAGCGCGAGTTACTTTCCGCTGCGATGCTCTGCCTAGGAAGCGTCCCAAATACCGGAGACCTTATTGAGCTGGCAAGGGCCTGTCTCACTATGATAGTCACATGCAAGAAGAGTGCAACTAATACTGAGAGAATGGTTTTCTCAGTAGTGCAGGCACCCCAAGTGCTGCAAAGCTGTAGGGTTGTGGCAAACAAATACTCATCAGTGAATGCAGTCAAGCACGTGAAAGCGCCAGAGAAGATTCCCGGGAGTGGAACCCTAGAATACAAGGTGAACTTTGTCTCCTTGACTGTGGTACCGAAGAAGGATGTCTACAAGATCCCAGCTGCAGTATTGAAGGTTTCTGGCTCGAGTCTGTACAATCTTGCGCTCAATGTCACTATTAATGTGGAGGTAGACCCGAGGAGTCCTTTGGTTAAATCTTTGTCTAAGTCTGACAGCGGATACTATGCTAACCTCTTCTTGCATATTGGACTTATGACCACCGTAGATAGGAAGGGGAAGAAAGTGACATTTGACAAGCTGGAAAAGAAAATAAGGAGCCTTGATCTATCTGTCGGGCTCAGTGATGTGCTCGGGCCTTCCGTGTTGGTAAAAGCAAGAGGTGCACGGACTAAGCTTTTGGCACCTTTCTTCTCTAGCAGTGGGACAGCCTGCTATCCCATAGCAAATGCTTCTCCTCAGGTGGCCAAGATACTCTGGAGTCAAACCGCGTGCCTGCGGAGCGTTAAAATCATTATCCAAGCAGGTACCCAACGCGCTGTCGCAGTGACCGCCGACCACGAGGTTACCTCTACTAAGCTGGAGAAGGGGCACACCCTTGCCAAATACAATCCTTTTAAGAAATAAGCTGCGTCTCTGAGATTGCGCTCCGCCCACTCACCCAGATCATCATGACACAAAAAACTAATCTGTCTTGATTATTTACAGTTAGTTTACCTGTCTATCAAGTTAGAAAAAACACGGGTAGAAGATTCTGGATCCCGGTTGGCGCCCTCCAGGTGCAAGttaattaaATGGGCTCCAGACCTTCTACCAAGAACCCAGCACCTATGATGCTGACTATCCGGGTTGCGCTGGTACTGAGTTGCATCTGTCCGGCAAACTCCATTGATGGCAGGCCTCTTGCAGCTGCAGGAATTGTGGTTACAGGAGACAAAGCCGTCAACATATACACCTCATCCCAGACAGGATCAATCATAGTTAAGCTCCTCCCGAATCTGCCCAAGGATAAGGAGGCATGTGCGAAAGCCCCCTTGGATGCATACAACAGGACATTGACCACTTTGCTCACCCCCCTTGGTGACTCTATCCGTAGGATACAAGAGTCTGTGACTACATCTGGAGGGGGGAGACAGGGGCGCCTTATAGGCGCCATTATTGGCGGTGTGGCTCTTGGGGTTGCAACTGCCGCACAAATAACAGCGGCCGCAGCTCTGATACAAGCCAAACAAAATGCTGCCAACATCCTCCGACTTAAAGAGAGCATTGCCGCAACCAATGAGGCTGTGCATGAGGTCACTGACGGATTATCGCAACTAGCAGTGGCAGTTGGGAAGATGCAGCAGTTTGTTAATGACCAATTTAATAAAACAGCTCAGGAATTAGACTGCATCAAAATTGCACAGCAAGTTGGTGTAGAGCTCAACCTGTACCTAACCGAATTGACTACAGTATTCGGACCACAAATCACTTCACCTGCTTTAAACAAGCTGACTATTCAGGCACTTTACAATCTAGCTGGTGGAAATATGGATTACTTATTGACTAAGTTAGGTGTAGGGAACAATCAACTCAGCTCATTAATCGGTAGCGGCTTAATCACtGGcAACCCTATTCTATACGACTCACAGACTCAACTCTTGGGTATACAGGTAACTgcaCCTTCAGTCGGGAACCTAAATAATATGCGTGCCACCTACTTGGAAACCTTATCCGTAAGCACAACCAGGGGATTTGCCTCGGCACTTGTCCCCAAAGTGGTGACACAGGTCGGTTCTGTGATAGAAGAACTTGACACCTCATACTGTATAGAAACTGACTTAGATTTATATTGTACAAGAATAGTAACGTTCCCTATGTCCCCTGGTATTTATTCCTGCTTGAGCGGCAATACGTCGGCCTGTATGTACTCAAAGACCGAAGGCGCACTTACTACACCATACATGACTATCAAAGGTTCAGTCATCGCCAACTGCAAGATGACAACATGTAGATGTGTAAACCCCCCGGGTATCATATCGCAAAACTATGGAGAAGCCGTGTCTCTAATAGATAAACAATCATGCAATGTTTTATCCTTAGGCGGGATAACTTTAAGGCTCAGTGGGGAATTCGATGTAACTTATCAGAAGAATATGTCAATACAAGATTCTCAAGTAATAATAACAGGCAATCTTGATATCTCAACTGAGGTTGGGAATGTCAACAACTCGATCAGTAATGCTTTGAATAAGTTAGAGGAAAGCAACAGAAAACTAGACAAAGTCAATGTCAAACTGACTAGCACATCTGCTCTCATTACgTATATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTGATTCTAGCATGCTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTTATTATGGCTTGGGAATAATACaCTcGATCAGATGAGAGCCACTACAAAAATGTGAACACAGATGAGGAACGAAGGTTTCCCTAATAGTAATTTGTGTGAAAGTTCTGGTAGTCTGTCAGTTCAGAGAGTTAAGAAAAAACTACCGGTTGTAGATGACCAAAGGACGATATACGGGTAGAACGGTAAGAGAGGCCGCCCCTCAATTGCGAGCCAGGCTTCACAACCTCCGTTCTACCGCTTCACCGACAACAGTCCTCAATCATGGACCGCGCCGTTAGCCAAGTTGCGTTAGAGAATGATGAAAGAGAGGCAAAAAATACATGGCGCTTGATATTCCGGATTGCAATCTTATTCTTAACAGTAGTGACCTTGGCTATATCTGTAGCCTCCCTTTTATATAGCATGGGGGCTAGCACACCTAGCGATCTTGTAGGCATACCGACTAGGATTTCCAGGGCAGAAGAAAAGATTACATCTACACTTGGTTCCAATCAAGATGTAGTAGATAGGATATATAAGCAAGTGGCCCTTGAGTCTCCGTTGGCATTGTTAAATACTGAGACCACAATTATGAACGCAATAACATCTCTCTCTTATCAGATTAATGGAGCTGCAAACAACAGTGGGTGGGGGGCACCTATCCATGACCCAGATTATATAGGGGGGATAGGCAAAGAACTCATTGTAGATGATGCTAGTGATGTCACATCATTCTATCCCTCTGCATTTCAAGAACATCTGAATTTTATCCCGGCGCCTACTACAGGATCAGGTTGCACTCGAATACCCTCATTTGACATGAGTGCTACCCATTACTGCTACACCCATAATGTAATATTGTCTGGATGCAGAGATCACTCACATTCATATCAGTATTTAGCACTTGGTGTGCTCCGGACATCTGCAACAGGGAGGGTATTCTTTTCTACTCTGCGTTCCATCAACCTGGACGACACCCAAAATCGGAAGTCTTGCAGTGTGAGTGCAACTCCCCTGGGTTGTGATATGCTGTGCTCGAAAGTCACGGAGACAGAGGAAGAAGATTATAACTCAGCTGTCCCTACGCGGATGGTACATGGGAGGTTAGGGTTCGACGGCCAGTACCACGAAAAGGACCTAGATGTCACAACATTATTCGGGGACTGGGTGGCCAACTACCCAGGAGTAGGGGGTGGATCTTTTATTGACAGCCGCGTATGGTTCTCAGTCTACGGAGGGTTAAAACCCAATTCACCCAGTGACACTGTACAGGAAGGGAAATATGTGATATACAAGCGATACAATGACACATGCCCAGATGAGCAAGACTACCAGATTCGAATGGCCAAGTCTTCGTATAAGCCTGGACGGTTTGGTGGGAAACGCATACAGCAGGCTATCTTATCTATCAAGGTGTCAACATCCTTAGGCGAAGACCCGGTACTGACTGTACCGCCCAACACAGTCACACTCATGGGGGCCGAAGGCAGAATTCTCACAGTAGGGACATCTCATTTCTTGTATCAACGAGGGTCATCATACTTCTCTCCCGCGTTATTATATCCTATGACAGTCAGCAACAAAACAGCCACTCTTCATAGTCCTTATACATTCAATGCCTTCACTCGGCCAGGTAGTATCCCTTGCCAGGCTTCAGCAAGATGCCCCAACTCGTGTGTTACTGGAGTCTATACAGATCCATATCCCCTAATCTTCTATAGAAACCACACCTTGCGAGGGGTATTCGGGACAATGCTTGATGGTGTACAAGCAAGACTTAACCCTGCGTCTGCAGTATTCGATAGCACATCCCGCAGTCGCATTACTCGAGTGAGTTCAAGCAGTACCAAAGCAGCATACACAACATCAACTTGTTTTAAAGTGGTCAAGACTAATAAGACCTATTGTCTCAGCATTGCTGAAATATCTAATACTCTCTTCGGAGAATTCAGAATCGTCCCGTTACTAGTTGAGATCCTCAAAGATGACGGGGTTAGAGAAGCCAGGTCTGGCTAGggcgcgccTTGAGTCAATTATAAAGGAGTTGGAAAGATGGCATTGTATCACCTATCTTCTGCGACATCAAGAATCAAACCGAATGCCGGCGCGTGCTCGAATTCCATGTTGCCAGTTGACCACAATCAGCCAGTGCTCATGCGATCAGATTAAGCCTTGTCATTAATCTCTTGATTAAGAAAAAATGTAAGTGGCAATGAGATACAAGGCAAAACAGCTCATGGTAAATAATACGGGTAGGACATGGCGAGCTCCGGTCCTGAAAGGGCAGAGCATCAGATTATCCTACCAGAGCCACACCTGTCTTCACCATTGGTCAAGCACAAACTACTCTATTACTGGAAATTAACTGGGCTACCGCTTCCTGATGAATGTGACTTCGACCACCTCATTCTCAGCCGACAATGGAAAAAAATACTTGAATCGGCCTCTCCTGATACTGAGAGAATGATAAAACTCGGAAGGGCAGTACACCAAACTCTTAACCACAATTCCAGAATAACCGGAGTGCTCCACCCCAGGTGTTTAGAACAACTGGCTAATATTGAGGTCCCAGATTCAACCAACAAATTTCGGAAGATTGAGAAGAAGATCCAAATTCACAACACGAGATATGGAGAACTGTTCACAAGGCTGTGTACGCATATAGAGAAGAAACTGCTGGGGTCATCTTGGTCTAACAATGTCCCCCGGTCAGAGGAGTTCAGCAGCATTCGTACGGATCCGGCATTCTGGTTTCACTCAAAATGGTCCACAGCCAAGTTTGCATGGCTCCATATAAAACAGATCCAGAGGCATCTGATGGTGGCAGCTAAGACAAGGTCTGCGGCCAACAAATTGGTGATGCTAACCCATAAGGTAGGCCAAGTCTTTGTCACTCCTGAACTTGTCGTTGTGACGCATACGAATGAGAACAAGTTCACATGTCTTACCCAGGAACTTGTATTGATGTATGCAGATATGATGGAGGGCAGAGATATGGTCAACATAATATCAACCACGGCGGTGCATCTCAGAAGCTTATCAGAGAAAATTGATGACATTTTGCGGTTAATAGACGCTCTGGCAAAAGACTTGGGTAATCAAGTCTACGATGTTGTATCACTAATGGAGGGATTTGCATACGGAGCTGTCCAGCTACTCGAGCCGTCAGGTACATTTGCAGGAGATTTCTTCGCATTCAACCTGCAGGAGCTTAAAGACATTCTAATTGGCCTCCTCCCCAATGATATAGCAGAATCCGTGACTCATGCAATCGCTACTGTATTCTCTGGTTTAGAACAGAATCAAGCAGCTGAGATGTTGTGTCTGTTGCGTCTGTGGGGTCACCCACTGCTTGAGTCCCGTATTGCAGCAAAGGCAGTCAGGAGCCAAATGTGCGCACCGAAAATGGTAGACTTTGATATGATCCTTCAGGTACTGTCTTTCTTCAAGGGAACAATCATCAACGGGTACAGAAAGAAGAATGCAGGTGTGTGGCCGCGAGTCAAAGTGGATACAATATATGGGAAGGTCATTGGGCAACTACATGCAGATTCAGCAGAGATTTCACACGATATCATGTTGAGAGAGTATAAGAGTTTATCTGCACTTGAATTTGAGCCATGTATAGAATATGACCCTGTCACCAACCTGAGCATGTTCCTAAAAGACAAGGCAATCGCACACCCCAACGATAATTGGCTTGCCTCGTTTAGGCGGAACCTTCTCTCCGAAGACCAGAAGAAACATGTAAAAGAAGCAACTTCGACTAATCGCCTCTTGATAGAGTTTTTAGAGTCAAATGATTTTGATCCATATAAAGAGATGGAATATCTGACGACCCTTGAGTACCTTAGAGATGACAATGTGGCAGTATCATACTCGCTCAAGGAGAAGGAAGTGAAAGTTAATGGACGGATCTTCGCTAAGCTGACAAAGAAGTTAAGGAACTGTCAGGTGATGGCGGAAGGGATCCTAGCCGATCAGATTGCACCTTTCTTTCAGGGAAATGGAGTCATTCAGGATAGCATATCCTTGACCAAGAGTATGCTAGCGATGAGTCAACTGTCTTTTAACAGCAATAAGAAACGTATCACTGACTGTAAAGAAAGAGTATCTTCAAACCGCAATCATGATCCGAAAAGCAAGAACCGTCGGAGAGTTGCAACCTTCATAACAACTGACCTGCAAAAGTACTGTCTTAATTGGAGATATCAGACAATCAAATTGTTCGCTCATGCCATCAATCAGTTGATGGGCCTACCTCACTTCTTCGAATGGATTCACCTAAGACTGATGGACACTACGATGTTCGTAGGAGACCCTTTCAATCCTCCAAGTGACCCTACTGACTGTGACCTCTCAAGAGTCCCTAATGATGACATATATATTGTCAGTGCCAGAGGGGGTATCGAAGGATTATGCCAGAAGCTATGGACAATGATCTCAATTGCTGCAATCCAACTTGCTGCAGCTAGATCGCATTGTCGTGTTGCCTGTATGGTACAGGGTGATAATCAAGTAATAGCAGTAACGAGAGAGGTAAGATCAGACGACTCTCCGGAGATGGTGTTGACACAGTTGCATCAAGCCAGTGATAATTTCTTCAAGGAATTAATTCATGTCAATCATTTGATTGGCCATAATTTGAAGGATCGTGAAACCATCAGGTCAGACACATTCTTCATATACAGCAAACGAATCTTCAAAGATGGAGCAATCCTCAGTCAAGTCCTCAAAAATTCATCTAAATTAGTGCTAGTGTCAGGTGATCTCAGTGAAAACACCGTAATGTCCTGTGCCAACATTGCCTCTACTGTAGCACGGCTATGCGAGAACGGGCTTCCCAAAGACTTCTGTTACTATTTAAACTATATAATGAGTTGTGTGCAGACATACTTTGACTCTGAGTTCTCCATCACCAACAATTCGCACCCCGATCTTAATCAGTCGTGGATTGAGGACATCTCTTTTGTGCACTCATATGTTCTGACTCCTGCCCAATTAGGGGGACTGAGTAACCTTCAATACTCAAGGCTCTACACTAGAAATATCGGTGACCCGGGGACTACTGCTTTTGCAGAGATCAAGCGACTAGAAGCAGTGGGATTACTGAGTCCTAACATTATGACTAATATCTTAACTAGGCCGCCTGGGAATGGAGATTGGGCCAGTCTGTGCAACGACCCATACTCTTTCAATTTTGAGACTGTTGCAAGCCCAAATATTGTTCTTAAGAAACATACGCAAAGAGTCCTATTTGAAACTTGTTCAAATCCCTTATTGTCTGGAGTGCACACAGAGGATAATGAGGCAGAAGAGAAGGCATTGGCTGAATTCTTGCTTAATCAAGAGGTGATTCATCCCCGCGTTGCGCATGCCATCATGGAGGCAAGCTCTGTAGGTAGGAGAAAGCAAATTCAAGGGCTTGTTGACACAACAAACACCGTAATTAAGATTGCGCTTACTAGGAGGCCATTAGGCATCAAGAGGCTGATGCGGATAGTCAATTATTCTAGCATGCATGCAATGCTGTTTAGAGACGATGTTTTTTCCTCCAGTAGATCCAACCACCCCTTAGTCTCTTCTAATATGTGTTCTCTGACACTGGCAGACTATGCACGGAATAGAAGCTGGTCACCTTTGACGGGAGGCAGGAAAATACTGGGTGTATCTAATCCTGATACGATAGAACTCGTAGAGGGTGAGATTCTTAGTGTAAGCGGAGGGTGTACAAGATGTGACAGCGGAGATGAACAATTTACTTGGTTCCATCTTCCAAGCAATATAGAATTGACCGATGACACCAGCAAGAATCCTCCGATGAGGGTACCATATCTCGGGTCAAAGACACAGGAGAGGAGAGCTGCCTCACTTGCAAAAATAGCTCATATGTCGCCACATGTAAAGGCTGCCCTAAGGGCATCATCCGTGTTGATCTGGGCTTATGGGGATAATGAAGTAAATTGGACTGCTGCTCTTACGATTGCAAAATCTCGGTGTAATGTAAACTTAGAGTATCTTCGGTTACTGTCCCCTTTACCCACGGCTGGGAATCTTCAACATAGACTAGATGATGGTATAACTCAGATGACATTCACCCCTGCATCTCTCTACAGGgtgtcaccttacattcacatatccaatgattctcaaaggctgttcactgaagaaggagtcaaagaggggaatgtggtttaccaacagatcATGCTCTTGGGTTTATCTCTAATCGAATCGATCTTTCCAATGACAACAACCAGGACATATGATGAGATCACACTGCACCTACATAGTAAATTTAGTTGCTGTATCAGAGAAGCACCTGTTGCGGTTCCTTTCGAGCTACTTGGGGTGGTACCGGAACTGAGGACAGTGACCTCAAATAAGTTTATGTATGATCCTAGCCCTGTATCGGAGGGAGACTTTGCGAGACTTGACTTAGCTATCTTCAAGAGTTATGAGCTTAATCTGGAGTCATATCCCACGATAGAGCTAATGAACATTCTTTCAATATCCAGCGGGAAGTTGATTGGCCAGTCTGTGGTTTCTTATGATGAAGATACCTCCATAAAGAATGACGCCATAATAGTGTATGACAATACCCGAAATTGGATCAGTGAAGCTCAGAATTCAGATGTGGTCCGCCTATTTGAATATGCAGCACTTGAAGTGCTCCTCGACTGTTCTTACCAACTCTATTACCTGAGAGTAAGAGGCCTAGACAATATTGTCTTATATATGGGTGATTTATACAAGAATATGCCAGGAATTCTACTTTCCAACATTGCAGCTACAATATCTCATCCCGTCATTCATTCAAGGTTACATGCAGTGGGCCTGGTCAACCATGACGGATCACACCAACTTGCAGATACGGATTTTATCGAAATGTCTGCAAAACTATTAGTATCTTGCACCCGACGTGTGATCTCCGGCTTATATTCAGGAAATAAGTATGATCTGCTGTTCCCATCTGTCTTAGATGATAACCTGAATGAGAAGATGCTTCAGCTGATATCCCGGTTATGCTGTCTGTACACGGTACTCTTTGCTACAACAAGAGAAATCCCGAAAATAAGAGGCTTAACTGCAGAAGAGAAATGTTCAATACTCACTGAGTATTTACTGTCGGATGCTGTGAAACCATTACTTAGCCCCGATCAAGTGAGCTCTATCATGTCTCCTAACATAATTACATTCCCAGCTAATCTGTACTACATGTCTCGGAAGAGCCTCAATTTGATCAGGGAAAGGGAGGACAGGGATACTATCCTGGCGTTGTTGTTCCCCCAAGAGCCATTATTAGAGTTCCCTTCTGTGCAAGATATTGGTGCTCGAGTGAAAGATCCATTCACCCGACAACCTGCGGCATTTTTGCAAGAGTTAGATTTGAGTGCTCCAGCAAGGTATGACGCATTCACACTTAGTCAGATTCATCCTGAACTCACATCTCCAAATCCGGAGGAAGACTACTTAGTACGATACTTGTTCAGAGGGATAGGGACTGCATCTTCCTCTTGGTATAAGGCATCTCATCTCCTTTCTGTACCCGAGGTAAGATGTGCAAGACACGGGAACTCCTTATACTTAGCTGAAGGGAGCGGAGCCATCATGAGTCTTCTCGAACTGCATGTACCACATGAAACTATCTATTACAATACGCTCTTTTCAAATGAGATGAACCCCCCGCAACGACATTTCGGGCCGACCCCAACTCAGTTTTTGAATTCGGTTGTTTATAGGAATCTACAGGCGGAGGTAACATGCAAAGATGGATTTGTCCAAGAGTTCCGTCCATTATGGAGAGAAAATACAGAGGAAAGTGACCTGACCTCAGATAAAGCAGTGGGGTATATTACATCTGCAGTGCCCTACAGATCTGTATCATTGCTGCATTGTGACATTGAAATTCCTCCAGGGTCCAATCAAAGCTTACTAGATCAACTAGCTATCAATTTATCTCTGATTGCCATGCATTCTGTAAGGGAGGGCGGGGTAGTAATCATCAAAGTGTTGTATGCAATGGGATACTACTTTCATCTACTCATGAACTTGTTTGCTCCGTGTTCCACAAAAGGATATATTCTCTCTAATGGTTATGCATGTCGAGGAGATATGGAGTGTTACCTGGTATTTGTCATGGGTTACCTGGGCGGGCCTACATTTGTACATGAGGTGGTGAGGATGGCAAAAACTCTGGTGCAGCGGCACGGTACGCTCTTGTCTAAATCAGATGAGATCACACTGACCAGGTTATTCACCTCACAGCGGCAGCGTGTGACAGACATCCTATCCAGTCCTTTACCAAGATTAATAAAGTACTTGAGGAAGAATATTGACACTGCGCTGATTGAAGCCGGGGGACAGCCCGTCCGTCCATTCTGTGCGGAGAGTCTGGTGAGCACGCTAGCGAACATAACTCAGATAACCCAGATTATCGCTAGTCACATTGACACAGTTATCCGGTCTGTGATATATATGGAAGCTGAGGGTGATCTCGCTGACACAGTATTTCTATTTACCCCTTACAATCTCTCTACTGACGGGAAAAAGAGGACATCACTTATACAGTGCACGAGACAGATCCTAGAGGTTACAATACTAGGTCTTAGAGTCGAAAATCTCAATAAAATAGGCGATATAATCAGCCTAGTGCTTAAAGGCATGATCTCCATGGAGGACCTTATCCCACTAAGGACATACTTGAAGCATAGTACCTGCCCTAAATATTTGAAGGCTGTCCTAGGTATTACCAAACTCAAAGAAATGTTTACAGACACTTCTGTATTGTACTTGACTCGTGCTCAACAAAAATTCTACATGAAAACTATAGGCAATGCAGTCAAAGGATATTACAGTAACTGTGACTCTTAACGAAAATCACATATTAATAGGCTCCTTTTTTGGCCAATTGTATTCTTGTTGATTTAATCATATTATGTTAGAAAAAAGTTGAACCCTGACTCCTTAGGACTCGAATTCGAACTCAAATAAATGTCTTAAAAAAAGGTTGCGCACAATTATTCTTGAGTGTAGTCTCGTCATTCACCAAATCTTTGTTTGGTGGCCGGCATGGTCCCAGCCTCCTCGCTGGCGCCGGCTGGGCAACATTCCGAGGGGACCGTCCCCTCGGTAATGGCGAATGGGACGTCGACTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTATAT SEQ ID NO:TAATACGACTCACTATAGGGACCAAACAGAGAATCCGTGAGTTACGATAAAAGGCGAAGG 4; NDV-AGCAATTGAAGTCGCACGGGTAGAAGGTGTGAATCTCGAGTGCGAGCCCGAAGCACAAAC COVID19-TCGAGAAAGCCTTCTGCCAACATGTCTTCCGTATTTGATGAGTACGAACAGCTCCTCGCG PrefusionGCTCAGACTCGCCCCAATGGAGCTCATGGAGGGGGAGAAAAAGGGAGTACCTTAAAAGTA Chimeric SGACGTCCCGGTATTCACTCTTAACAGTGATGACCCAGAAGATAGATGGAGCTTTGTGGTA MolecularTTCTGCCTCCGGATTGCTGTTAGCGAAGATGCCAACAAACCACTCAGGCAAGGTGCTCTC CloneATATCTCTTTTATGCTCCCACTCACAGGTAATGAGGAACCATGTTGCCATTGCAGGGAAA AF077761.1_CAGAATGAAGCCACATTGGCCGTGCTTGAGATTGATGGCTTTGCCAACGGCACGCCCCAG LaSota_KanTTCAACAATAGGAGTGGAGTGTCTGAAGAGAGAGCACAGAGATTTGCGATGATAGCAGGA R (withTCTCTCCCTCGGGCATGCAGCAACGGAACCCCGTTCGTCACAGCCGGGGCAGAAGATGAT stabilizingGCACCAGAAGACATCACCGATACCCTGGAGAGGATCCTCTCTATCCAGGCTCAAGTATGG sequence inGTCACAGTAGCAAAAGCCATGACTGCGTATGAGACTGCAGATGAGTCGGAAACAAGGCGA L)ATCAATAAGTATATGCAGCAAGGCAGGGTCCAAAAGAAATACATCCTCTACCCCGTATGC Sequence ofAGGAGCACAATCCAACTCACGATCAGACAGTCTCTTGCAGTCCGCATCTTTTTGGTTAGC the Pre-GAGCTCAAGAGAGGCCGCAACACGGCAGGTGGTACCTCTACTTATTATAACCTGGTAGGG fusionGACGTAGACTCATACATCAGGAATACCGGGCTTACTGCATTCTTCTTGACACTCAAGTAC stabilizedGGAATCAACACCAAGACATCAGCCCTTGCACTTAGTAGCCTCTCAGGCGACATCCAGAAG (HexaPro)ATGAAGCAGCTCATGCGTTTGTATCGGATGAAAGGAGATAATGCGCCGTACATGACATTA withCTTGGTGATAGTGACCAGATGAGCTTTGCGCCTGCCGAGTATGCACAACTTTACTCCTTT cytoplasmicGCCATGGGTATGGCATCAGTCCTAGATAAAGGTACTGGGAAATACCAATTTGCCAGGGAC andTTTATGAGCACATCATTCTGGAGACTTGGAGTAGAGTACGCTCAGGCTCAGGGAAGTAGCtransmembraneATTAACGAGGATATGGCTGCCGAGCTAAAGCTAACCCCAGCAGCAATGAAGGGCCTGGCA domainsGCTGCTGCCCAACGGGTCTCCGACGATACCAGCAGCATATACATGCCTACTCAACAAGTC from NDVGGAGTCCTCACTGGGCTTAGCGAGGGGGGGTCCCAAGCTCTACAAGGCGGATCGAATAGATCGCAAGGGCAACCAGAAGCCGGGGATGGGGAGACCCAATTCCTGGATCTGATGAGAGCGGTAGCAAATAGCATGAGGGAGGCGCCAAACTCTGCACAGGGCACTCCCCAATCGGGGCCTCCCCCAACTCCTGGGCCATCCCAAGATAACGACACCGACTGGGGGTATTGATGGACAAAACCCAGCCTGCTTCCACAAAAACATCCCAATGCCCTCACCCGTAGTCGACCCCTCGATTTGCGGCTCTATATGACCACACCCTCAAACAAACATCCCCCTCTTTCCTCCCTCCCCCTGCTGTACAACTCCGCACGCCCTAGATACCACAGGCACAATGCGGCTCACTAACAATCAAAACAGAGCCGAGGGAATTAGAAAAAAGTACGGGTAGAAGAGGGATATTCAGAGATCAGGGCAAGTCTCCCGAGTCTCTGCTCTCTCCTCTACCTGATAGACCAGGACAAACATGGCCACCTTTACAGATGCAGAGATCGACGAGCTATTTGAGACAAGTGGAACTGTCATTGACAACATAATTACAGCCCAGGGTAAACCAGCAGAGACTGTTGGAAGGAGTGCAATCCCACAAGGCAAGACCAAGGTGCTGAGCGCAGCATGGGAGAAGCATGGGAGCATCCAGCCACCGGCCAGTCAAGACAACCCCGATCGACAGGACAGATCTGACAAACAACCATCCACACCCGAGCAAACGACCCCGCATGACAGCCCGCCGGCCACATCCGCCGACCAGCCCCCCACCCAGGCCACAGACGAAGCCGTCGACACACAGTTCAGGACCGGAGCAAGCAACTCTCTGCTGTTGATGCTTGACAAGCTCAGCAATAAATCGTCCAATGCTAAAAAGGGCCCATGGTCGAGCCCCCAAGAGGGGAATCACCAACGTCCGACTCAACAGCAGGGGAGTCAACCCAGTCGCGGAAACAGTCAGGAAAGACCGCAGAACCAAGTCAAGGCCGCCCCTGGAAACCAGGGCACAGACGTGAACACAGCATATCATGGACAATGGGAGGAGTCACAACTATCAGCTGGTGCAACCCCTCATGCTCTCCGATCAAGGCAGAGCCAAGACAATACCCTTGTATCTGCGGATCATGTCCAGCCACCTGTAGACTTTGTGCAAGCGATGATGTCTATGATGGAGGCGATATCACAGAGAGTAAGTAAGGTTGACTATCAGCTAGATCTTGTCTTGAAACAGACATCCTCCATCCCTATGATGCGGTCCGAAATCCAACAGCTGAAAACATCTGTTGCAGTCATGGAAGCCAACTTGGGAATGATGAAGATTCTGGATCCCGGTTGTGCCAACATTTCATCTCTGAGTGATCTACGGGCAGTTGCCCGATCTCACCCGGTTTTAGTTTCAGGCCCTGGAGACCCCTCTCCCTATGTGACACAAGGAGGCGAAATGGCACTTAATAAACTTTCGCAACCAGTGCCACATCCATCTGAATTGATTAAACCCGCCACTGCATGCGGGCCTGATATAGGAGTGGAAAAGGACACTGTCCGTGCATTGATCATGTCACGCCCAATGCACCCGAGTTCTTCAGCCAAGCTCCTAAGCAAGTTAGATGCAGCCGGGTCGATCGAGGAAATCAGGAAAATCAAGCGCCTTGCTCTAAATGGCTAATTACTACTGCCACACGTAGCGGGTCCCTGTCCACTCGGCATCACACGGAATCTGCACCGAGTTCCCCCtctagaTTAGAAAAAATACGGGTAGAACCGCCACCATGTTCGTGTTCCTGGTCCTGCTGCCACTGGTAAGCTCCCAATGTGTAAACTTAACCACAAGAACCCAGCTCCCACCTGCCTACACCAACAGCTTCACCAGAGGCGTTTATTACCCCGACAAGGTATTCCGGTCTTCTGTTCTGCACTCTACCCAGGACCTGTTTCTGCCCTTTTTCAGCAACGTGACATGGTTCCACGCCATCCACGTGTCTGGCACAAACGGCACCAAGCGGTTTGATAATCCTGTGCTCCCTTTCAATGACGGCGTGTACTTCGCCTCTACTGAGAAGAGCAACATCATCCGGGGCTGGATCTTTGGCACAACACTGGACTCTAAAACCCAGAGCCTGCTGATCGTGAACAACGCCACCAACGTGGTGATTAAGGTGTGCGAGTTCCAGTTCTGCAATGACCCTTTCCTCGGCGTGTACTACCACAAGAACAACAAAAGTTGGATGGAAAGCGAATTCAGGGTGTACTCAAGCGCCAACAACTGTACCTTCGAGTACGTGAGCCAGCCTTTCCTGATGGACCTAGAAGGTAAGCAGGGCAATTTCAAGAACCTCAGAGAGTTCGTGTTCAAGAATATTGACGGCTACTTCAAAATCTACAGCAAGCACACCCCAATCAACCTGGTGCGGGACCTGCCCCAGGGCTTTAGCGCGCTGGAGCCTCTGGTGGACCTGCCTATCGGCATCAACATCACCCGGTTCCAGACACTGCTGGCTCTGCATAGAAGCTACCTGACACCTGGCGACAGTTCTTCTGGCTGGACAGCCGGCGCCGCCGCCTACTACGTGGGCTACCTGCAGCCTAGAACATTCCTGCTGAAATACAACGAGAACGGCACGATCACAGACGCCGTGGACTGCGCCCTGGATCCCCTGTCTGAGACAAAGTGCACCCTGAAGTCTTTCACCGTGGAGAAGGGCATCTACCAGACCTCCAACTTCAGAGTGCAGCCTACCGAATCCATCGTGCGCTTTCCCAACATCACCAACCTGTGCCCCTTCGGCGAGGTCTTTAATGCCACGAGATTCGCCAGCGTGTATGCCTGGAACAGAAAGAGAATCAGCAACTGCGTGGCCGACTACAGCGTGCTGTACAACAGCGCCTCTTTCAGCACATTTAAGTGCTACGGAGTGTCTCCTACCAAACTCAACGATCTGTGCTTCACGAACGTGTATGCCGACAGCTTCGTGATCCGAGGAGATGAGGTGCGGCAGATCGCTCCAGGACAGACAGGCAAGATCGCCGACTACAACTACAAGCTGCCCGACGACTTTACCGGCTGCGTGATCGCTTGGAACAGCAATAACCTGGACTCAAAGGTTGGAGGAAACTACAACTACCTGTACAGACTGTTCAGAAAGTCCAACCTGAAGCCCTTCGAGAGAGACATCTCTACAGAAATCTACCAGGCCGGCAGCACCCCATGTAACGGCGTGGAAGGCTTCAACTGCTACTTCCCTCTGCAGTCTTATGGCTTCCAGCCCACAAACGGAGTGGGCTATCAGCCTTACCGCGTGGTTGTCCTGAGCTTTGAGCTGCTGCATGCCCCTGCTACGGTGTGTGGACCTAAGAAGTCCACCAACCTGGTGAAGAACAAGTGTGTGAACTTCAACTTCAACGGCCTGACCGGCACCGGGGTGCTGACAGAGTCTAACAAGAAATTCCTGCCATTCCAGCAATTCGGCCGGGACATCGCCGACACCACCGACGCCGTGCGGGATCCTCAGACCCTCGAAATCCTGGACATCACCCCCTGTAGCTTCGGCGGCGTGAGCGTGATCACCCCTGGCACAAACACCAGCAATCAAGTGGCTGTCCTGTACCAGGATGTCAATTGCACAGAAGTGCCTGTGGCCATCCACGCCGATCAGCTGACCCCCACCTGGCGGGTGTACTCGACAGGAAGCAACGTGTTTCAAACAAGAGCCGGCTGCCTGATCGGGGCCGAGCACGTGAACAATTCCTACGAGTGCGACATCCCCATCGGCGCCGGCATCTGTGCCTCTTACCAGACACAGACCAATTCCCCTggtagtgcaagtTCCGTGGCCAGCCAGAGCATCATCGCCTACACCATGAGCCTGGGCGCCGAAAACAGCGTTGCATATTCCAACAACAGCATCGCCATCCCTACCAACTTCACCATCAGCGTGACCACAGAAATCCTGCCTGTGTCCATGACCAAGACAAGCGTTGATTGCACCATGTACATCTGCGGCGATAGCACAGAGTGCAGCAATCTGCTGCTGCAGTACGGTAGCTTCTGCACCCAGCTGAATAGAGCCCTGACCGGCATCGCTGTGGAACAGGACAAAAACACCCAGGAGGTCTTCGCCCAGGTGAAGCAAATCTACAAGACCCCTCCAATCAAGGACTTCGGAGGCTTTAACTTTAGCCAGATCCTGCCTGATCCCTCCAAGCCTAGCAAACGGAGTcctATCGAGGACCTGCTCTTCAACAAGGTGACCCTGGCTGACGCCGGCTTCATTAAGCAGTACGGCGATTGCCTCGGCGACATCGCTGCAAGAGACCTGATCTGCGCCCAGAAGTTCAACGGCCTGACCGTGCTGCCTCCTCTCCTGACAGACGAGATGATCGCCCAGTACACCTCTGCCCTTCTGGCTGGCACCATCACCAGCGGATGGACCTTTGGAGCCGGAcctGCCCTGCAGATCCCTTTCcctATGCAGATGGCCTACAGATTCAACGGGATCGGAGTGACCCAAAACGTGCTGTATGAAAACCAGAAACTGATCGCCAATCAGTTTAACAGCGCCATCGGCAAAATCCAGGATAGCCTGTCCAGCACCccaAGCGCCCTCGGCAAGCTGCAAGATGTGGTGAATCAAAATGCCCAAGCCCTGAACACACTGGTGAAGCAGCTGAGCAGCAACTTCGGCGCCATCAGCAGCGTGCTGAACGACATCCTGAGCAGACTGGACccacctGAAGCCGAGGTGCAGATCGACAGACTGATCACAGGCAGACTGCAGTCCCTGCAGACCTACGTGACCCAGCAGTTGATTAGAGCCGCTGAGATTAGAGCCAGTGCCAACCTGGCTGCCACAAAGATGTCAGAATGCGTGCTGGGCCAGAGCAAGAGAGTGGACTTCTGCGGCAAAGGCTACCACCTGATGAGCTTTCCTCAGTCTGCACCCCACGGCGTGGTGTTTCTCCACGTGACATACGTGCCCGCGCAAGAAAAGAACTTTACAACCGCCCCAGCGATCTGCCACGACGGCAAGGCCCACTTCCCTCGGGAGGGTGTGTTCGTGAGCAATGGAACACACTGGTTCGTCACCCAGCGGAACTTCTACGAGCCTCAGATCATTACCACCGACAACACCTTCGTGAGCGGCAACTGTGACGTCGTTATCGGCATCGTGAACAATACCGTGTACGACCCCCTGCAGCCTGAGCTGGATAGCTTCAAAGAGGAACTGGACAAGTACTTCAAGAACCACACAAGCCCCGACGTGGACCTAGGCGACATCTCTGGAATCAACGCCAGCGTGGTGAACATCCAAAAGGAAATCGACAGACTGAACGAGGTGGCCAAGAATCTGAATGAAAGCCTGATCGATCTGCAGGAGCTGGGCAAGTACGAGCAGggtggcggtggctcgCTGATTACCTATATCGTCCTGACTATTATCTCCCTGGTGTTTGGCATTCTGTCCCTGATTCTGGCCTGTTACCTGATGTACAAGCAGAAGGCCCAGCAGAAGACCCTGCTGTGGCTGGGCAATAATACACTGGATCAGATGCGGGCTACAACTAAGATGTGAacgcgtACCCAAGGTCCAACTCTCCAAGCGGCAATCCTCTCTCGCTTCCTCAGCCCCACTGAATGGTCGCGTAACCGTAATTAATCTAGCTACATTTAAGATTAAGAAAAAATACGGGTAGAATTGGAGTGCCCCAATTGTGCCAAGATGGACTCATCTAGGACAATTGGGCTGTACTTTGATTCTGCCCATTCTTCTAGCAACCTGTTAGCATTTCCGATCGTCCTACAAGGCACAGGAGATGGGAAGAAGCAAATCGCCCCGCAATATAGGATCCAGCGCCTTGACTTGTGGACTGATAGTAAGGAGGACTCAGTATTCATCACCACCTATGGATTCATCTTTCAAGTTGGGAATGAAGAAGCCACTGTCGGCATGATCGATGATAAACCCAAGCGCGAGTTACTTTCCGCTGCGATGCTCTGCCTAGGAAGCGTCCCAAATACCGGAGACCTTATTGAGCTGGCAAGGGCCTGTCTCACTATGATAGTCACATGCAAGAAGAGTGCAACTAATACTGAGAGAATGGTTTTCTCAGTAGTGCAGGCACCCCAAGTGCTGCAAAGCTGTAGGGTTGTGGCAAACAAATACTCATCAGTGAATGCAGTCAAGCACGTGAAAGCGCCAGAGAAGATTCCCGGGAGTGGAACCCTAGAATACAAGGTGAACTTTGTCTCCTTGACTGTGGTACCGAAGAAGGATGTCTACAAGATCCCAGCTGCAGTATTGAAGGTTTCTGGCTCGAGTCTGTACAATCTTGCGCTCAATGTCACTATTAATGTGGAGGTAGACCCGAGGAGTCCTTTGGTTAAATCTTTGTCTAAGTCTGACAGCGGATACTATGCTAACCTCTTCTTGCATATTGGACTTATGACCACCGTAGATAGGAAGGGGAAGAAAGTGACATTTGACAAGCTGGAAAAGAAAATAAGGAGCCTTGATCTATCTGTCGGGCTCAGTGATGTGCTCGGGCCTTCCGTGTTGGTAAAAGCAAGAGGTGCACGGACTAAGCTTTTGGCACCTTTCTTCTCTAGCAGTGGGACAGCCTGCTATCCCATAGCAAATGCTTCTCCTCAGGTGGCCAAGATACTCTGGAGTCAAACCGCGTGCCTGCGGAGCGTTAAAATCATTATCCAAGCAGGTACCCAACGCGCTGTCGCAGTGACCGCCGACCACGAGGTTACCTCTACTAAGCTGGAGAAGGGGCACACCCTTGCCAAATACAATCCTTTTAAGAAATAAGCTGCGTCTCTGAGATTGCGCTCCGCCCACTCACCCAGATCATCATGACACAAAAAACTAATCTGTCTTGATTATTTACAGTTAGTTTACCTGTCTATCAAGTTAGAAAAAACACGGGTAGAAGATTCTGGATCCCGGTTGGCGCCCTCCAGGTGCAAGttaattaaATGGGCTCCAGACCTTCTACCAAGAACCCAGCACCTATGATGCTGACTATCCGGGTTGCGCTGGTACTGAGTTGCATCTGTCCGGCAAACTCCATTGATGGCAGGCCTCTTGCAGCTGCAGGAATTGTGGTTACAGGAGACAAAGCCGTCAACATATACACCTCATCCCAGACAGGATCAATCATAGTTAAGCTCCTCCCGAATCTGCCCAAGGATAAGGAGGCATGTGCGAAAGCCCCCTTGGATGCATACAACAGGACATTGACCACTTTGCTCACCCCCCTTGGTGACTCTATCCGTAGGATACAAGAGTCTGTGACTACATCTGGAGGGGGGAGACAGGGGCGCCTTATAGGCGCCATTATTGGCGGTGTGGCTCTTGGGGTTGCAACTGCCGCACAAATAACAGCGGCCGCAGCTCTGATACAAGCCAAACAAAATGCTGCCAACATCCTCCGACTTAAAGAGAGCATTGCCGCAACCAATGAGGCTGTGCATGAGGTCACTGACGGATTATCGCAACTAGCAGTGGCAGTTGGGAAGATGCAGCAGTTTGTTAATGACCAATTTAATAAAACAGCTCAGGAATTAGACTGCATCAAAATTGCACAGCAAGTTGGTGTAGAGCTCAACCTGTACCTAACCGAATTGACTACAGTATTCGGACCACAAATCACTTCACCTGCTTTAAACAAGCTGACTATTCAGGCACTTTACAATCTAGCTGGTGGAAATATGGATTACTTATTGACTAAGTTAGGTGTAGGGAACAATCAACTCAGCTCATTAATCGGTAGCGGCTTAATCACtGGcAACCCTATTCTATACGACTCACAGACTCAACTCTTGGGTATACAGGTAACTgcaCCTTCAGTCGGGAACCTAAATAATATGCGTGCCACCTACTTGGAAACCTTATCCGTAAGCACAACCAGGGGATTTGCCTCGGCACTTGTCCCCAAAGTGGTGACACAGGTCGGTTCTGTGATAGAAGAACTTGACACCTCATACTGTATAGAAACTGACTTAGATTTATATTGTACAAGAATAGTAACGTTCCCTATGTCCCCTGGTATTTATTCCTGCTTGAGCGGCAATACGTCGGCCTGTATGTACTCAAAGACCGAAGGCGCACTTACTACACCATACATGACTATCAAAGGTTCAGTCATCGCCAACTGCAAGATGACAACATGTAGATGTGTAAACCCCCCGGGTATCATATCGCAAAACTATGGAGAAGCCGTGTCTCTAATAGATAAACAATCATGCAATGTTTTATCCTTAGGCGGGATAACTTTAAGGCTCAGTGGGGAATTCGATGTAACTTATCAGAAGAATATCTCAATACAAGATTCTCAAGTAATAATAACAGGCAATCTTGATATCTCAACTGAGCTTGGGAATGTCAACAACTCGATCAGTAATGCTTTGAATAAGTTAGAGGAAAGCAACAGAAAACTAGACAAAGTCAATGTCAAACTGACTAGCACATCTGCTCTCATTACgTATATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTGATTCTAGCATGCTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTTATTATGGCTTGGGAATAATACaCTcGATCAGATGAGAGCCACTACAAAAATGTGAACACAGATGAGGAACGAAGGTTTCCCTAATAGTAATTTGTGTGAAAGTTCTGGTAGTCTGTCAGTTCAGAGAGTTAAGAAAAAACTACCGGTTGTAGATGACCAAAGGACGATATACGGGTAGAACGGTAAGAGAGGCCGCCCCTCAATTGCGAGCCAGGCTTCACAACCTCCGTTCTACCGCTTCACCGACAACAGTCCTCAATCATGGACCGCGCCGTTAGCCAAGTTGCGTTAGAGAATGATGAAAGAGAGGCAAAAAATACATGGCGCTTGATATTCCGGATTGCAATCTTATTCTTAACAGTAGTGACCTTGGCTATATCTGTAGCCTCCCTTTTATATAGCATGGGGGCTAGCACACCTAGCGATCTTGTAGGCATACCGACTAGGATTTCCAGGGCAGAAGAAAAGATTACATCTACACTTGGTTCCAATCAAGATGTAGTAGATAGGATATATAAGCAAGTGGCCCTTGAGTCTCCGTTGGCATTGTTAAATACTGAGACCACAATTATGAACGCAATAACATCTCTCTCTTATCAGATTAATGGAGCTGCAAACAACAGTGGGTGGGGGGCACCTATCCATGACCCAGATTATATAGGGGGGATAGGCAAAGAACTCATTGTAGATGATGCTAGTGATGTCACATCATTCTATCCCTCTGCATTTCAAGAACATCTGAATTTTATCCCGGCGCCTACTACAGGATCAGGTTGCACTCGAATACCCTCATTTGACATGAGTGCTACCCATTACTGCTACACCCATAATGTAATATTGTCTGGATGCAGAGATCACTCACATTCATATCAGTATTTAGCACTTGGTGTGCTCCGGACATCTGCAACAGGGAGGGTATTCTTTTCTACTCTGCGTTCCATCAACCTGGACGACACCCAAAATCGGAAGTCTTGCAGTGTGAGTGCAACTCCCCTGGGTTGTGATATGCTGTGCTCGAAAGTCACGGAGACAGAGGAAGAAGATTATAACTCAGCTGTCCCTACGCGGATGGTACATGGGAGGTTAGGGTTCGACGGCCAGTACCACGAAAAGGACCTAGATGTCACAACATTATTCGGGGACTGGGTGGCCAACTACCCAGGAGTAGGGGGTGGATCTTTTATTGACAGCCGCGTATGGTTCTCAGTCTACGGAGGGTTAAAACCCAATTCACCCAGTGACACTGTACAGGAAGGGAAATATGTGATATACAAGCGATACAATGACACATGCCCAGATGAGCAAGACTACCAGATTCGAATGGCCAAGTCTTCGTATAAGCCTGGACGGTTTGGTGGGAAACGCATACAGCAGGCTATCTTATCTATCAAGGTGTCAACATCCTTAGGCGAAGACCCGGTACTGACTGTACCGCCCAACACAGTCACACTCATGGGGGCCGAAGGCAGAATTCTCACAGTAGGGACATCTCATTTCTTGTATCAACGAGGGTCATCATACTTCTCTCCCGCGTTATTATATCCTATGACAGTCAGCAACAAAACAGCCACTCTTCATAGTCCTTATACATTCAATGCCTTCACTCGGCCAGGTAGTATCCCTTGCCAGGCTTCAGCAAGATGCCCCAACTCGTGTGTTACTGGAGTCTATACAGATCCATATCCCCTAATCTTCTATAGAAACCACACCTTGCGAGGGGTATTCGGGACAATGCTTGATGGTGTACAAGCAAGACTTAACCCTGCGTCTGCAGTATTCGATAGCACATCCCGCAGTCGCATTACTCGAGTGAGTTCAAGCAGTACCAAAGCAGCATACACAACATCAACTTGTTTTAAAGTGGTCAAGACTAATAAGACCTATTGTCTCAGCATTGOTGAAATATCTAATACTCTCTTCGGAGAATTCAGAATCGTCCCGTTACTAGTTGAGATCCTCAAAGATGACGGGGTTAGAGAAGCCAGGTCTGGCTAGggcgcgccTTGAGTCAATTATAAAGGAGTTGGAAAGATGGCATTGTATCACCTATCTTCTGCGACATCAAGAATCAAACCGAATGCCGGCGCGTGCTCGAATTCCATGTTGCCAGTTGACCACAATCAGCCAGTGCTCATGCGATCAGATTAAGCCTTGTCATTAATCTCTTGATTAAGAAAAAATGTAAGTGGCAATGAGATACAAGGCAAAACAGCTCATGGTAAATAATACGGGTAGGACATGGCGAGCTCCGGTCCTGAAAGGGCAGAGCATCAGATTATCCTACCAGAGCCACACCTGTCTTCACCATTGGTCAAGCACAAACTACTCTATTACTGGAAATTAACTGGGCTACCGCTTCCTGATGAATGTGACTTCGACCACCTCATTCTCAGCCGACAATGGAAAAAAATACTTGAATCGGCCTCTCCTGATACTGAGAGAATGATAAAACTCGGAAGGGCAGTACACCAAACTCTTAACCACAATTCCAGAATAACCGGAGTGCTCCACCCCAGGTGTTTAGAACAACTGGCTAATATTGAGGTCCCAGATTCAACCAACAAATTTCGGAAGATTGAGAAGAAGATCCAAATTCACAACACGAGATATGGAGAACTGTTCACAAGGCTGTGTACGCATATAGAGAAGAAACTGCTGGGGTCATCTTGGTCTAACAATGTCCCCCGGTCAGAGGAGTTCAGCAGCATTCGTACGGATCCGGCATTCTGGTTTCACTCAAAATGGTCCACAGCCAAGTTTGCATGGCTCCATATAAAACAGATCCAGAGGCATCTGATGGTGGCAGCTAAGACAAGGTCTGCGGCCAACAAATTGGTGATGCTAACCCATAAGGTAGGCCAAGTCTTTGTCACTCCTGAACTTGTCGTTGTGACGCATACGAATGAGAACAAGTTCACATGTCTTACCCAGGAACTTGTATTGATGTATGCAGATATGATGGAGGGCAGAGATATGGTCAACATAATATCAACCACGGCGGTGCATCTCAGAAGCTTATCAGAGAAAATTGATGACATTTTGCGGTTAATAGACGCTCTGGCAAAAGACTTGGGTAATCAAGTCTACGATGTTGTATCACTAATGGAGGGATTTGCATACGGAGCTGTCCAGCTACTCGAGCCGTCAGGTACATTTGCAGGAGATTTCTTCGCATTCAACCTGCAGGAGCTTAAAGACATTCTAATTGGCCTCCTCCCCAATGATATAGCAGAATCCGTGACTCATGCAATCGCTACTGTATTCTCTGGTTTAGAACAGAATCAAGCAGCTGAGATGTTGTGTCTGTTGCGTCTGTGGGGTCACCCACTGCTTGAGTCCCGTATTGCAGCAAAGGCAGTCAGGAGCCAAATGTGCGCACCGAAAATGGTAGACTTTGATATGATCCTTCAGGTACTGTCTTTCTTCAAGGGAACAATCATCAACGGGTACAGAAAGAAGAATGCAGGTGTGTGGCCGCGAGTCAAAGTGGATACAATATATGGGAAGGTCATTGGGCAACTACATGCAGATTCAGCAGAGATTTCACACGATATCATGTTGAGAGAGTATAAGAGTTTATCTGCACTTGAATTTGAGCCATGTATAGAATATGACCCTGTCACCAACCTGAGCATGTTCCTAAAAGACAAGGCAATCGCACACCCCAACGATAATTGGCTTGCCTCGTTTAGGCGGAACCTTCTCTCCGAAGACCAGAAGAAACATGTAAAAGAAGCAACTTCGACTAATCGCCTCTTGATAGAGTTTTTAGAGTCAAATGATTTTGATCCATATAAAGAGATGGAATATCTGACGACCCTTGAGTACCTTAGAGATGACAATGTGGCAGTATCATACTCGCTCAAGGAGAAGGAAGTGAAAGTTAATGGACGGATCTTCGCTAAGCTGACAAAGAAGTTAAGGAACTGTCAGGTGATGGCGGAAGGGATCCTAGCCGATCAGATTGCACCTTTCTTTCAGGGAAATGGAGTCATTCAGGATAGCATATCCTTGACCAAGAGTATGCTAGCGATGAGTCAACTGTCTTTTAACAGCAATAAGAAACGTATCACTGACTGTAAAGAAAGAGTATCTTCAAACCGCAATCATGATCCGAAAAGCAAGAACCGTCGGAGAGTTGCAACCTTCATAACAACTGACCTGCAAAAGTACTGTCTTAATTGGAGATATCAGACAATCAAATTGTTCGCTCATGCCATCAATCAGTTGATGGGCCTACCTCACTTCTTCGAATGGATTCACCTAAGACTGATGGACACTACGATGTTCGTAGGAGACCCTTTCAATCCTCCAAGTGACCCTACTGACTGTGACCTCTCAAGAGTCCCTAATGATGACATATATATTGTCAGTGCCAGAGGGGGTATCGAAGGATTATGCCAGAAGCTATGGACAATGATCTCAATTGCTGCAATCCAACTTGCTGCAGCTAGATCGCATTGTCGTGTTGCCTGTATGGTACAGGGTGATAATCAAGTAATAGCAGTAACGAGAGAGGTAAGATCAGACGACTCTCCGGAGATGGTGTTGACACAGTTGCATCAAGCCAGTGATAATTTCTTCAAGGAATTAATTCATGTCAATCATTTGATTGGCCATAATTTGAAGGATCGTGAAACCATCAGGTCAGACACATTCTTCATATACAGCAAACGAATCTTCAAAGATGGAGCAATCCTCAGTCAAGTCCTCAAAAATTCATCTAAATTAGTGCTAGTGTCAGGTGATCTCAGTGAAAACACCGTAATGTCCTGTGCCAACATTGCCTCTACTGTAGCACGGCTATGCGAGAACGGGCTTCCCAAAGACTTCTGTTACTATTTAAACTATATAATGAGTTGTGTGCAGACATACTTTGACTCTGAGTTCTCCATCACCAACAATTCGCACCCCGATCTTAATCAGTCGTGGATTGAGGACATCTCTTTTGTGCACTCATATGTTCTGACTCCTGCCCAATTAGGGGGACTGAGTAACCTTCAATACTCAAGGCTCTACACTAGAAATATCGGTGACCCGGGGACTACTGCTTTTGCAGAGATCAAGCGACTAGAAGCAGTGGGATTACTGAGTCCTAACATTATGACTAATATCTTAACTAGGCCGCCTGGGAATGGAGATTGGGCCAGTCTGTGCAACGACCCATACTCTTTCAATTTTGAGACTGTTGCAAGCCCAAATATTGTTCTTAAGAAACATACGCAAAGAGTCCTATTTGAAACTTGTTCAAATCCCTTATTGTCTGGAGTGCACACAGAGGATAATGAGGCAGAAGAGAAGGCATTGGCTGAATTCTTGCTTAATCAAGAGGTGATTCATCCCCGCGTTGCGCATGCCATCATGGAGGCAAGCTCTGTAGGTAGGAGAAAGCAAATTCAAGGGCTTGTTGACACAACAAACACCGTAATTAAGATTGCGCTTACTAGGAGGCCATTAGGCATCAAGAGGCTGATGCGGATAGTCAATTATTCTAGCATGCATGCAATGCTGTTTAGAGACGATGTTTTTTCCTCCAGTAGATCCAACCACCCCTTAGTCTCTTCTAATATGTGTTCTCTGACACTGGCAGACTATGCACGGAATAGAAGCTGGTCACCTTTGACGGGAGGCAGGAAAATACTGGGTGTATCTAATCCTGATACGATAGAACTCGTAGAGGGTGAGATTCTTAGTGTAAGCGGAGGGTGTACAAGATGTGACAGCGGAGATGAACAATTTACTTGGTTCCATCTTCCAAGCAATATAGAATTGACCGATGACACCAGCAAGAATCCTCCGATGAGGGTACCATATCTCGGGTCAAAGACACAGGAGAGGAGAGCTGCCTCACTTGCAAAAATAGCTCATATGTCGCCACATGTAAAGGCTGCCCTAAGGGCATCATCCGTGTTGATCTGGGCTTATGGGGATAATGAAGTAAATTGGACTGCTGCTCTTACGATTGCAAAATCTCGGTGTAATGTAAACTTAGAGTATCTTCGGTTACTGTCCCCTTTACCCACGGCTGGGAATCTTCAACATAGACTAGATGATGGTATAACTCAGATGACATTCACCCCTGCATCTCTCTACAGGgtgtcaccttacattcacatatccaatgattctcaaaggctgttcactgaagaaggagtcaaagaggggaatgtggtttaccaacagatcATGCTCTTGGGTTTATCTCTAATCGAATCGATCTTTCCAATGACAACAACCAGGACATATGATGAGATCACACTGCACCTACATAGTAAATTTAGTTGCTGTATCAGAGAAGCACCTGTTGCGGTTCCTTTCGAGCTACTTGGGGTGGTACCGGAACTGAGGACAGTGACCTCAAATAAGTTTATGTATGATCCTAGCCCTGTATCGGAGGGAGACTTTGCGAGACTTGACTTAGCTATCTTCAAGAGTTATGAGCTTAATCTGGAGTCATATCCCACGATAGAGCTAATGAACATTCTTTCAATATCCAGCGGGAAGTTGATTGGCCAGTCTGTGGTTTCTTATGATGAAGATACCTCCATAAAGAATGACGCCATAATAGTGTATGACAATACCCGAAATTGGATCAGTGAAGCTCAGAATTCAGATGTGGTCCGCCTATTTGAATATGCAGCACTTGAAGTGCTCCTCGACTGTTCTTACCAACTCTATTACCTGAGAGTAAGAGGCCTAGACAATATTGTCTTATATATGGGTGATTTATACAAGAATATGCCAGGAATTCTACTTTCCAACATTGCAGCTACAATATCTCATCCCGTCATTCATTCAAGGTTACATGCAGTGGGCCTGGTCAACCATGACGGATCACACCAACTTGCAGATACGGATTTTATCGAAATGTCTGCAAAACTATTAGTATCTTGCACCCGACGTGTGATCTCCGGCTTATATTCAGGAAATAAGTATGATCTGCTGTTCCCATCTGTCTTAGATGATAACCTGAATGAGAAGATGCTTCAGCTGATATCCCGGTTATGCTGTCTGTACACGGTACTCTTTGCTACAACAAGAGAAATCCCGAAAATAAGAGGCTTAACTGCAGAAGAGAAATGTTCAATACTCACTGAGTATTTACTGTCGGATGCTGTGAAACCATTACTTAGCCCCGATCAAGTGAGCTCTATCATGTCTCCTAACATAATTACATTCCCAGCTAATCTGTACTACATGTCTCGGAAGAGCCTCAATTTGATCAGGGAAAGGGAGGACAGGGATACTATCCTGGCGTTGTTGTTCCCCCAAGAGCCATTATTAGAGTTCCCTTCTGTGCAAGATATTGGTGCTCGAGTGAAAGATCCATTCACCCGACAACCTGCGGCATTTTTGCAAGAGTTAGATTTGAGTGCTCCAGCAAGGTATGACGCATTCACACTTAGTCAGATTCATCCTGAACTCACATCTCCAAATCCGGAGGAAGACTACTTAGTACGATACTTGTTCAGAGGGATAGGGACTGCATCTTCCTCTTGGTATAAGGCATCTCATCTCCTTTCTGTACCCGAGGTAAGATGTGCAAGACACGGGAACTCCTTATACTTAGCTGAAGGGAGCGGAGCCATCATGAGTCTTCTCGAACTGCATGTACCACATGAAACTATCTATTACAATACGCTCTTTTCAAATGAGATGAACCCCCCGCAACGACATTTCGGGCCGACCCCAACTCAGTTTTTGAATTCGGTTGTTTATAGGAATCTACAGGCGGAGGTAACATGCAAAGATGGATTTGTCCAAGAGTTCCGTCCATTATGGAGAGAAAATACAGAGGAAAGTGACCTGACCTCAGATAAAGCAGTGGGGTATATTACATCTGCAGTGCCCTACAGATCTGTATCATTGCTGCATTGTGACATTGAAATTCCTCCAGGGTCCAATCAAAGCTTACTAGATCAACTAGCTATCAATTTATCTCTGATTGCCATGCATTCTGTAAGGGAGGGCGGGGTAGTAATCATCAAAGTGTTGTATGCAATGGGATACTACTTTCATCTACTCATGAACTTGTTTGCTCCGTGTTCCACAAAAGGATATATTCTCTCTAATGGTTATGCATGTCGAGGAGATATGGAGTGTTACCTGGTATTTGTCATGGGTTACCTGGGCGGGCCTACATTTGTACATGAGGTGGTGAGGATGGCAAAAACTCTGGTGCAGCGGCACGGTACGCTCTTGTCTAAATCAGATGAGATCACACTGACCAGGTTATTCACCTCACAGCGGCAGCGTGTGACAGACATCCTATCCAGTCCTTTACCAAGATTAATAAAGTACTTGAGGAAGAATATTGACACTGCGCTGATTGAAGCCGGGGGACAGCCCGTCCGTCCATTCTGTGCGGAGAGTCTGGTGAGCACGCTAGCGAACATAACTCAGATAACCCAGATTATCGCTAGTCACATTGACACAGTTATCCGGTCTGTGATATATATGGAAGCTGAGGGTGATCTCGCTGACACAGTATTTCTATTTACCCCTTACAATCTCTCTACTGACGGGAAAAAGAGGACATCACTTATACAGTGCACGAGACAGATCCTAGAGGTTACAATACTAGGTCTTAGAGTCGAAAATCTCAATAAAATAGGCGATATAATCAGCCTAGTGCTTAAAGGCATGATCTCCATGGAGGACCTTATCCCACTAAGGACATACTTGAAGCATAGTACCTGCCCTAAATATTTGAAGGCTGTCCTAGGTATTACCAAACTCAAAGAAATGTTTACAGACACTTCTGTATTGTACTTGACTCGTGCTCAACAAAAATTCTACATGAAAACTATAGGCAATGCAGTCAAAGGATATTACAGTAACTGTGACTCTTAACGAAAATCACATATTAATAGGCTCCTTTTTTGGCCAATTGTATTCTTGTTGATTTAATCATATTATGTTAGAAAAAAGTTGAACCCTGACTCCTTAGGACTCGAATTCGAACTCAAATAAATGTCTTAAAAAAAGGTTGCGCACAATTATTCTTGAGTGTAGTCTCGTCATTCACCAAATCTTTGTTTGGTGGCCGGCATGGTCCCAGCCTCCTCGCTGGCGCCGGCTGGGCAACATTCCGAGGGGACCGTCCCCTCGGTAATGGCGAATGGGACGTCGACTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGA GGAACTATASEQ ID NO: TAATACGACTCACTATAGGGACCAAACAGAGAATCCGTGAGTTACGATAAAAGGCGAAGG5; NDV- AGCAATTGAAGTCGCACGGGTAGAAGGTGTGAATCTCGAGTGCGAGCCCGAAGCACAAACAPMV5 F-HN TCGAGAAAGCCTTCTGCCAACATGTCTTCCGTATTTGATGAGTACGAACAGCTCCTCGCGChimeric - GCTCAGACTCGCCCCAATGGAGCTCATGGAGGGGGAGAAAAAGGGAGTACCTTAAAAGTAexpressing GACGTCCCGGTATTCACTCTTAACAGTGATGACCCAGAAGATAGATGGAGCTTTGTGGTAGFP TTCTGCCTCCGGATTGCTGTTAGCGAAGATGCCAACAAACCACTCAGGCAAGGTGCTCTCATATCTCTTTTATGCTCCCACTCACAGGTAATGAGGAACCATGTTGCCATTGCAGGGAAACAGAATGAAGCCACATTGGCCGTGCTTGAGATTGATGGCTTTGCCAACGGCACGCCCCAGTTCAACAATAGGAGTGGAGTGTCTGAAGAGAGAGCACAGAGATTTGCGATGATAGCAGGATCTCTCCCTCGGGCATGCAGCAACGGAACCCCGTTCGTCACAGCCGGGGCAGAAGATGATGCACCAGAAGACATCACCGATACCCTGGAGAGGATCCTCTCTATCCAGGCTCAAGTATGGGTCACAGTAGCAAAAGCCATGACTGCGTATGAGACTGCAGATGAGTCGGAAACAAGGCGAATCAATAAGTATATGCAGCAAGGCAGGGTCCAAAAGAAATACATCCTCTACCCCGTATGCAGGAGCACAATCCAACTCACGATCAGACAGTCTCTTGCAGTCCGCATCTTTTTGGTTAGCGAGCTCAAGAGAGGCCGCAACACGGCAGGTGGTACCTCTACTTATTATAACCTGGTAGGGGACGTAGACTCATACATCAGGAATACCGGGCTTACTGCATTCTTCTTGACACTCAAGTACGGAATCAACACCAAGACATCAGCCCTTGCACTTAGTAGCCTCTCAGGCGACATCCAGAAGATGAAGCAGCTCATGCGTTTGTATCGGATGAAAGGAGATAATGCGCCGTACATGACATTACTTGGTGATAGTGACCAGATGAGCTTTGCGCCTGCCGAGTATGCACAACTTTACTCCTTTGCCATGGGTATGGCATCAGTCCTAGATAAAGGTACTGGGAAATACCAATTTGCCAGGGACTTTATGAGCACATCATTCTGGAGACTTGGAGTAGAGTACGCTCAGGCTCAGGGAAGTAGCATTAACGAGGATATGGCTGCCGAGCTAAAGCTAACCCCAGCAGCAATGAAGGGCCTGGCAGCTGCTGCCCAACGGGTCTCCGACGATACCAGCAGCATATACATGCCTACTCAACAAGTCGGAGTCCTCACTGGGCTTAGCGAGGGGGGGTCCCAAGCTCTACAAGGCGGATCGAATAGATCGCAAGGGCAACCAGAAGCCGGGGATGGGGAGACCCAATTCCTGGATCTGATGAGAGCGGTAGCAAATAGCATGAGGGAGGCGCCAAACTCTGCACAGGGCACTCCCCAATCGGGGCCTCCCCCAACTCCTGGGCCATCCCAAGATAACGACACCGACTGGGGGTATTGATGGACAAAACCCAGCCTGCTTCCACAAAAACATCCCAATGCCCTCACCCGTAGTCGACCCCTCGATTTGCGGCTCTATATGACCACACCCTCAAACAAACATCCCCCTCTTTCCTCCCTCCCCCTGCTGTACAACTCCGCACGCCCTAGATACCACAGGCACAATGCGGCTCACTAACAATCAAAACAGAGCCGAGGGAATTAGAAAAAAGTACGGGTAGAAGAGGGATATTCAGAGATCAGGGCAAGTCTCCCGAGTCTCTGCTCTCTCCTCTACCTGATAGACCAGGACAAACATGGCCACCTTTACAGATGCAGAGATCGACGAGCTATTTGAGACAAGTGGAACTGTCATTGACAACATAATTACAGCCCAGGGTAAACCAGCAGAGACTGTTGGAAGGAGTGCAATCCCACAAGGCAAGACCAAGGTGCTGAGCGCAGCATGGGAGAAGCATGGGAGCATCCAGCCACCGGCCAGTCAAGACAACCCCGATCGACAGGACAGATCTGACAAACAACCATCCACACCCGAGCAAACGACCCCGCATGACAGCCCGCCGGCCACATCCGCCGACCAGCCCCCCACCCAGGCCACAGACGAAGCCGTCGACACACAGTTCAGGACCGGAGCAAGCAACTCTCTGCTGTTGATGCTTGACAAGCTCAGCAATAAATCGTCCAATGCTAAAAAGGGCCCATGGTCGAGCCCCCAAGAGGGGAATCACCAACGTCCGACTCAACAGCAGGGGAGTCAACCCAGTCGCGGAAACAGTCAGGAAAGACCGCAGAACCAAGTCAAGGCCGCCCCTGGAAACCAGGGCACAGACGTGAACACAGCATATCATGGACAATGGGAGGAGTCACAACTATCAGCTGGTGCAACCCCTCATGCTCTCCGATCAAGGCAGAGCCAAGACAATACCCTTGTATCTGCGGATCATGTCCAGCCACCTGTAGACTTTGTGCAAGCGATGATGTCTATGATGGAGGCGATATCACAGAGAGTAAGTAAGGTTGACTATCAGCTAGATCTTGTCTTGAAACAGACATCCTCCATCCCTATGATGCGGTCCGAAATCCAACAGCTGAAAACATCTGTTGCAGTCATGGAAGCCAACTTGGGAATGATGAAGATTCTGGATCCCGGTTGTGCCAACATTTCATCTCTGAGTGATCTACGGGCAGTTGCCCGATCTCACCCGGTTTTAGTTTCAGGCCCTGGAGACCCCTCTCCCTATGTGACACAAGGAGGCGAAATGGCACTTAATAAACTTTCGCAACCAGTGCCACATCCATCTGAATTGATTAAACCCGCCACTGCATGCGGGCCTGATATAGGAGTGGAAAAGGACACTGTCCGTGCATTGATCATGTCACGCCCAATGCACCCGAGTTCTTCAGCCAAGCTCCTAAGCAAGTTAGATGCAGCCGGGTCGATCGAGGAAATCAGGAAAATCAAGCGCCTTGCTCTAAATGGCTAATTACTACTGCCACACGTAGCGGGTCCCTGTCCACTCGGCATCACACGGAATCTGCACCGAGTTCCCCCtctagaTTAGAAAAAATACGGGTAGAACCGCCACCATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCGCCCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAGTaATaaacgcgtACCCAAGGTCCAACTCTCCAAGCGGCAATCCTCTCTCGCTTCCTCAGCCCCACTGAATGGTCGCGTAACCGTAATTAATCTAGCTACATTTAAGATTAAGAAAAAATACGGGTAGAATTGGAGTGCCCCAATTGTGCCAAGATGGACTCATCTAGGACAATTGGGCTGTACTTTGATTCTGCCCATTCTTCTAGCAACCTGTTAGCATTTCCGATCGTCCTACAAGGCACAGGAGATGGGAAGAAGCAAATCGCCCCGCAATATAGGATCCAGCGCCTTGACTTGTGGACTGATAGTAAGGAGGACTCAGTATTCATCACCACCTATGGATTCATCTTTCAAGTTGGGAATGAAGAAGCCACTGTCGGCATGATCGATGATAAACCCAAGCGCGAGTTACTTTCCGCTGCGATGCTCTGCCTAGGAAGCGTCCCAAATACCGGAGACCTTATTGAGCTGGCAAGGGCCTGTCTCACTATGATAGTCACATGCAAGAAGAGTGCAACTAATACTGAGAGAATGGTTTTCTCAGTAGTGCAGGCACCCCAAGTGCTGCAAAGCTGTAGGGTTGTGGCAAACAAATACTCATCAGTGAATGCAGTCAAGCACGTGAAAGCGCCAGAGAAGATTCCCGGGAGTGGAACCCTAGAATACAAGGTGAACTTTGTCTCCTTGACTGTGGTACCGAAGAAGGATGTCTACAAGATCCCAGCTGCAGTATTGAAGGTTTCTGGCTCGAGTCTGTACAATCTTGCGCTCAATGTCACTATTAATGTGGAGGTAGACCCGAGGAGTCCTTTGGTTAAATCTTTGTCTAAGTCTGACAGCGGATACTATGCTAACCTCTTCTTGCATATTGGACTTATGACCACCGTAGATAGGAAGGGGAAGAAAGTGACATTTGACAAGCTGGAAAAGAAAATAAGGAGCCTTGATCTATCTGTCGGGCTCAGTGATGTGCTCGGGCCTTCCGTGTTGGTAAAAGCAAGAGGTGCACGGACTAAGCTTTTGGCACCTTTCTTCTCTAGCAGTGGGACAGCCTGCTATCCCATAGCAAATGCTTCTCCTCAGGTGGCCAAGATACTCTGGAGTCAAACCGCGTGCCTGCGGAGCGTTAAAATCATTATCCAAGCAGGTACCCAACGCGCTGTCGCAGTGACCGCCGACCACGAGGTTACCTCTACTAAGCTGGAGAAGGGGCACACCCTTGCCAAATACAATCCTTTTAAGAAATAAGCTGCGTCTCTGAGATTGCGCTCCGCCCACTCACCCAGATCATCATGACACAAAAAACTAATCTGTCTTGATTATTTACAGTTAGTTTACCTGTCTATCAAGTTAGAAAAAACACGGGTAGAAGATTCTGGATCCCGGTTGGCGCCCTCCAGGTGCAAGttaattaaATGTTACAACTTCCCTTGACCATTCTTCTTAGCATTCTTAGTGCTCACCAGTCGCTTTGTCTAGACAACAGTAAGCTCATTCATGCAGGAATCATGAGTACTACTGAGAGAGAAGTTAATGTTTATGCACAATCTATTACTGGGTCAATAGTGGTGAGATTGATTCCAAATATCCCAAGTAACCATAAATCTTGTGCAACTAGCCAAATCAAATTATACAATGACACGTTAACAAGATTGTTGACCCCAATTAAAGCTAATCTAGAAGGACTTATTAGTGCTGTTTCTCAGGACCAATCGCAGAATTCTGGGAAGAGAAAGAAGCGTTTTGTAGGCGCAGTAATTGGAGCAGCTGCCCTTGGTTTGGCAACTGCTGCACAGGTGACTGCCACTGTAGCATTAAATCAAGCGCAAGAAAACGCTCGGAATATCCTAAGGCTTAAAAACTCGATTCAGAAGACAAACGAGGCGGTGATGGAACTTAAAGATGCTGTGGGCCAAACAGCAGTAGCTATTGACAAAACTCAGGCCTTCATAAATAATCAAATCTTGCCTGCAATTTCAAATCTCTCATGTGAGGTCCTAGGGAATAAAATTGGGGTCCAATTATCTTTGTACCTTACTGAATTAACAACAGTATTCGGCAACCAACTGACAAACCCAGCCCTTACCACACTGTCATTACAAGCCTTGTACAATCTTTGTGGAGATGACTTCAATTACTTAATCAACCTATTAAATGCAAAAAATCGTAACTTAGCCTCACTTTATGAAGCAAACCTAATTCAGGGGAGAATTACTCAATATGACTCAATGAATCAGTTATTAATTATTCAGGTACAAATACCAAGCATCTCCACAGTGTCAGGAATGAGGGTCACAGAATTGTTCACACTTAGTGTTGACACACCTATAGGAGAGGGAAAGGCCCTAGTACCAAAATATGTCCTATCCTCAGGGAGAATAATGGAAGAGGTTGACCTAAGCAGTTGCGCTATAACATCAACATCAGTTTTCTGTTCCTCTATCATCTCTAGACCCCTTCCACTTGAAACAATAAATTGCCTGAATGGGAATGTTACACAGTGTCAATTTACCGCCAACACAGGAACCCTTGAATCGAGATACGCTGTTATAGGAGGATTGGTGATTGCTAACTGTAAGGCTATAGTATGCAGGTGCCTAAATCCACCAGGTGTCATTGCGCAAAATCTTGGCTTACCAATTACAATCATCTCATCCAATACTTGTCAGCGAATTAATTTAGAACAAATCACTTTGTCTCTTGGGAACAGCATATTATCTACATACAGTGCCAATTTATCCCAAGTTGAGATGAATTTAGCTCCATCAAATCCTCTGGATATCTCAGTTGAATTGAATCGAGTCAACACCAGTCTCTCTAAAGTGGAATCTCTAATAAAAGAAAGCAATAGTATCCTGGACTCAGTAAACCCTCAAATTTTAAATGTCAAGACACTCATTACgTATATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTGATTCTAGCATGCTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTTATTATGGCTTGGGAATAATACaCTcGATCAGATGAGAGCCACTACAAAAATGTGAACACAGATGAGGAACGAAGGTTTCCCTAATAGTAATTTGTGTGAAAGTTCTGGTAGTCTGTCAGTTCAGAGAGTTAAGAAAAAACTACCGGTTGTAGATGACCAAAGGACGATATACGGGTAGAACGGTAAGAGAGGCCGCCCCTCAATTGCGAGCCAGGCTTCACAACCTCCGTTCTACCGCTTCACCGACAACAGTCCTCAATCATGGACCGCGCCGTTAGCCAAGTTGCGTTAGAGAATGATGAAAGAGAGGCAAAAAATACATGGCGCTTGATATTCCGGATTGCAATCTTATTCTTAACAGTAGTGACCTTGGCTATATCTGTAGCCTCCCTTTTATATAGCATGGGGGCTAGCACACCTTCCACTCTGATCAGCCTAAATAACTCAATTATCACAAGCAGCAATGGTCTCAAAAAGGAAATCCTGAACCAGAACATAAAAGAGGACCTCATATATAGAGAAGTTGCTATAAATATACCTTTAACATTAGATAGGGTTACTGTTGAGGTAGGGACTGCAGTAAACCAGATTACTGATGCACTCAGGCAACTCCAGTCAGTTAATGGATCTGCTGCATTCGCCTCATCAAACTCTCCTGATTATAGTGGGGGAATAGAACACCTGATTTTCCAAAGGAATACGCTTATTAATCGCTCAGTGAGTGTCTCAGATTTAATAGAACACCCCAGTTTCATACCAACTCCTACTACACAGCATGGTTGTACCAGAATCCCCACATTCCACCTAGGAACTCGCCACTGGTGCTATAGTCACAATATAATAGGTCAGGGATGTGCTGATTCTAGAGCTAGTGTGATGTATATTTCAATGGGAGCACTGGGTGTCAGTTCATTGGGAACCCCGACCTTCACAACATCTGCTGCATCAATATTATCTGATAGCCTCAATCGGAAGAGTTGCAGTATAGTAGCAACAACTGAGGGTTGTGACGTACTCTGCAGTATAGTTACACAAACAGAAGACCAAGATTATGCTGATCACACTCCTACTCCAATGATACATGGTAGATTATGGTTTAATGGCACATACACAGAGAGATCCTTATCCCAGAGTTTATTCCTTGGAACATGGGCTGCGCAATATCCGGCTGTAGGATCTGGTATAATGACACCTGGGCGAGTTATATTCCCTTTCTATGGAGGTGTGATCCCTAACTCTCCTCTCTTCTTGGATCTCGAAAGATTCGCTTTATTCACACATAATGGAGACTTAGAATGCATGAACTTAACACAATATCAGAAAGAAGCAATTTACTCTGCATATAAGCCTCCCAAGATTAGAGGATCACTGTGGGCACAAGGCTTCATAGTATGTTCAGTAGGAGACATGGGGAATTGCTCTCTTAAAGTGATCAATACAAGCACAGTTATGATGGGTGCAGAAGGTCGGCTACAATTAGTTGGGGACTCCGTTATGTACTATCAGAGATCATCATCCTGGTGGCCTGTAGGAATTCTTTATCGGTTGAGTCTTGTAGACATCATCGCCGGAGATATACAGGTCGTCATAAACAGTGAACCACTCCCTCTGAGCAAGTTCCCGCGGCCAACCTGGACTCCAGGAGTGTGTCAAAAACCAAATGTATGCCCTGCAGTTTGTGTAACTGGGGTCTATCAAGACCTTTGGGCAATTTCCGCAGGGGAGACACTATCTGAAATGACATTCTTTGGAGGATATTTAGAGGCATCCACCCAACGAAAAGATCCATGGATAGGCGTTGCTAATCAATATAGTTGGTTCATGAGAAGAAGATTATTCAAGACAAGCACTGAAGCTGCATATTCGTCATCAACGTGTTTTAGGAACACTAGACTGGATCGAAATTTCTGCCTATTAGTCTTTGAATTAACTGATAACTTACTTGGAGACTGGAGAATTGTCCCCCTCTTATTTGAATTAACCATCGTATAAggcgcgccTTGAGTCAATTATAAAGGAGTTGGAAAGATGGCATTGTATCACCTATCTTCTGCGACATCAAGAATCAAACCGAATGCCGGCGCGTGCTCGAATTCCATGTTGCCAGTTGACCACAATCAGCCAGTGCTCATGCGATCAGATTAAGCCTTGTCATTAATCTCTTGATTAAGAAAAAATGTAAGTGGCAATGAGATACAAGGCAAAACAGCTCATGGTAAATAATACGGGTAGGACATGGCGAGCTCCGGTCCTGAAAGGGCAGAGCATCAGATTATCCTACCAGAGCCACACCTGTCTTCACCATTGGTCAAGCACAAACTACTCTATTACTGGAAATTAACTGGGCTACCGCTTCCTGATGAATGTGACTTCGACCACCTCATTCTCAGCCGACAATGGAAAAAAATACTTGAATCGGCCTCTCCTGATACTGAGAGAATGATAAAACTCGGAAGGGCAGTACACCAAACTCTTAACCACAATTCCAGAATAACCGGAGTGCTCCACCCCAGGTGTTTAGAACAACTGGCTAATATTGAGGTCCCAGATTCAACCAACAAATTTCGGAAGATTGAGAAGAAGATCCAAATTCACAACACGAGATATGGAGAACTGTTCACAAGGCTGTGTACGCATATAGAGAAGAAACTGCTGGGGTCATCTTGGTCTAACAATGTCCCCCGGTCAGAGGAGTTCAGCAGCATTCGTACGGATCCGGCATTCTGGTTTCACTCAAAATGGTCCACAGCCAAGTTTGCATGGCTCCATATAAAACAGATCCAGAGGCATCTGATGGTGGCAGCTAAGACAAGGTCTGCGGCCAACAAATTGGTGATGCTAACCCATAAGGTAGGCCAAGTCTTTGTCACTCCTGAACTTGTCGTTGTGACGCATACGAATGAGAACAAGTTCACATGTCTTACCCAGGAACTTGTATTGATGTATGCAGATATGATGGAGGGCAGAGATATGGTCAACATAATATCAACCACGGCGGTGCATCTCAGAAGCTTATCAGAGAAAATTGATGACATTTTGCGGTTAATAGAGGCTCTGGCAAAAGACTTGGGTAATCAAGTCTACGATGTTGTATCACTAATGGAGGGATTTGCATACGGAGCTGTCCAGCTACTCGAGCCGTCAGGTACATTTGCAGGAGATTTCTTCGCATTCAACCTGCAGGAGCTTAAAGACATTCTAATTGGCCTCCTCCCCAATGATATAGCAGAATCCGTGACTCATGCAATCGCTACTGTATTCTCTGGTTTAGAACAGAATCAAGCAGCTGAGATGTTGTGTCTGTTGCGTCTGTGGGGTCACCCACTGCTTGAGTCCCGTATTGCAGCAAAGGCAGTCAGGAGCCAAATGTGCGCACCGAAAATGGTAGACTTTGATATGATCCTTCAGGTACTGTCTTTCTTCAAGGGAACAATCATCAACGGGTACAGAAAGAAGAATGCAGGTGTGTGGCCGCGAGTCAAAGTGGATACAATATATGGGAAGGTCATTGGGCAACTACATGCAGATTCAGCAGAGATTTCACACGATATCATGTTGAGAGAGTATAAGAGTTTATCTGCACTTGAATTTGAGCCATGTATAGAATATGACCCTGTCACCAACCTGAGCATGTTCCTAAAAGACAAGGCAATCGCACACCCCAACGATAATTGGCTTGCCTCGTTTAGGCGGAACCTTCTCTCCGAAGACCAGAAGAAACATGTAAAAGAAGCAACTTCGACTAATCGCCTCTTGATAGAGTTTTTAGAGTCAAATGATTTTGATCCATATAAAGAGATGGAATATCTGACGACCCTTGAGTACCTTAGAGATGACAATGTGGCAGTATCATACTCGCTCAAGGAGAAGGAAGTGAAAGTTAATGGACGGATCTTCGCTAAGCTGACAAAGAAGTTAAGGAACTGTCAGGTGATGGCGGAAGGGATCCTAGCCGATCAGATTGCACCTTTCTTTCAGGGAAATGGAGTCATTCAGGATAGCATATCCTTGACCAAGAGTATGCTAGCGATGAGTCAACTGTCTTTTAACAGCAATAAGAAACGTATCACTGACTGTAAAGAAAGAGTATCTTCAAACCGCAATCATGATCCGAAAAGCAAGAACCGTCGGAGAGTTGCAACCTTCATAACAACTGACCTGCAAAAGTACTGTCTTAATTGGAGATATCAGACAATCAAATTGTTCGCTCATGCCATCAATCAGTTGATGGGCCTACCTCACTTCTTCGAATGGATTCACCTAAGACTGATGGACACTACGATGTTCGTAGGAGACCCTTTCAATCCTCCAAGTGACCCTACTGACTGTGACCTCTCAAGAGTCCCTAATGATGACATATATATTGTCAGTGCCAGAGGGGGTATCGAAGGATTATGCCAGAAGCTATGGACAATGATCTCAATTGCTGCAATCCAACTTGCTGCAGCTAGATCGCATTGTCGTGTTGCCTGTATGGTACAGGGTGATAATCAAGTAATAGCAGTAACGAGAGAGGTAAGATCAGACGACTCTCCGGAGATGGTGTTGACACAGTTGCATCAAGCCAGTGATAATTTCTTCAAGGAATTAATTCATGTCAATCATTTGATTGGCCATAATTTGAAGGATCGTGAAACCATCAGGTCAGACACATTCTTCATATACAGCAAACGAATCTTCAAAGATGGAGCAATCCTCAGTCAAGTCCTCAAAAATTCATCTAAATTAGTGCTAGTGTCAGGTGATCTCAGTGAAAACACCGTAATGTCCTGTGCCAACATTGCCTCTACTGTAGCACGGCTATGCGAGAACGGGCTTCCCAAAGACTTCTGTTACTATTTAAACTATATAATGAGTTGTGTGCAGACATACTTTGACTCTGAGTTCTCCATCACCAACAATTCGCACCCCGATCTTAATCAGTCGTGGATTGAGGACATCTCTTTTGTGCACTCATATGTTCTGACTCCTGCCCAATTAGGGGGACTGAGTAACCTTCAATACTCAAGGCTCTACACTAGAAATATCGGTGACCCGGGGACTACTGCTTTTGCAGAGATCAAGCGACTAGAAGCAGTGGGATTACTGAGTCCTAACATTATGACTAATATCTTAACTAGGCCGCCTGGGAATGGAGATTGGGCCAGTCTGTGCAACGACCCATACTCTTTCAATTTTGAGACTGTTGCAAGCCCAAATATTGTTCTTAAGAAACATACGCAAAGAGTCCTATTTGAAACTTGTTCAAATCCCTTATTGTCTGGAGTGCACACAGAGGATAATGAGGCAGAAGAGAAGGCATTGGCTGAATTCTTGCTTAATCAAGAGGTGATTCATCCCCGCGTTGCGCATGCCATCATGGAGGCAAGCTCTGTAGGTAGGAGAAAGCAAATTCAAGGGCTTGTTGACACAACAAACACCGTAATTAAGATTGCGCTTACTAGGAGGCCATTAGGCATCAAGAGGCTGATGCGGATAGTCAATTATTCTAGCATGCATGCAATGCTGTTTAGAGACGATGTTTTTTCCTCCAGTAGATCCAACCACCCCTTAGTCTCTTCTAATATGTGTTCTCTGACACTGGCAGACTATGCACGGAATAGAAGCTGGTCACCTTTGACGGGAGGCAGGAAAATACTGGGTGTATCTAATCCTGATACGATAGAACTCGTAGAGGGTGAGATTCTTAGTGTAAGCGGAGGGTGTACAAGATGTGACAGCGGAGATGAACAATTTACTTGGTTCCATCTTCCAAGCAATATAGAATTGACCGATGACACCAGCAAGAATCCTCCGATGAGGGTACCATATCTCGGGTCAAAGACACAGGAGAGGAGAGCTGCCTCACTTGCAAAAATAGCTCATATGTCGCCACATGTAAAGGCTGCCCTAAGGGCATCATCCGTGTTGATCTGGGCTTATGGGGATAATGAAGTAAATTGGACTGCTGCTCTTACGATTGCAAAATCTCGGTGTAATGTAAACTTAGAGTATCTTCGGTTACTGTCCCCTTTACCCACGGCTGGGAATCTTCAACATAGACTAGATGATGGTATAACTCAGATGACATTCACCCCTGCATCTCTCTACAGGgtgtcaccttacattcacatatccaatgattctcaaaggctgttcactgaagaaggagtcaaagaggggaatgtggtttaccaacagatcATGCTCTTGGGTTTATCTCTAATCGAATCGATCTTTCCAATGACAACAACCAGGACATATGATGAGATCACACTGCACCTACATAGTAAATTTAGTTGCTGTATCAGAGAAGCACCTGTTGCGGTTCCTTTCGAGCTACTTGGGGTGGTACCGGAACTGAGGACAGTGACCTCAAATAAGTTTATGTATGATCCTAGCCCTGTATCGGAGGGAGACTTTGCGAGACTTGACTTAGCTATCTTCAAGAGTTATGAGCTTAATCTGGAGTCATATCCCACGATAGAGCTAATGAACATTCTTTCAATATCCAGCGGGAAGTTGATTGGCCAGTCTGTGGTTTCTTATGATGAAGATACCTCCATAAAGAATGACGCCATAATAGTGTATGACAATACCCGAAATTGGATCAGTGAAGCTCAGAATTCAGATGTGGTCCGCCTATTTGAATATGCAGCACTTGAAGTGCTCCTCGACTGTTCTTACCAACTCTATTACCTGAGAGTAAGAGGCCTAGACAATATTGTCTTATATATGGGTGATTTATACAAGAATATGCCAGGAATTCTACTTTCCAACATTGCAGCTACAATATCTCATCCCGTCATTCATTCAAGGTTACATGCAGTGGGCCTGGTCAACCATGACGGATCACACCAACTTGCAGATACGGATTTTATCGAAATGTCTGCAAAACTATTAGTATCTTGCACCCGACGTGTGATCTCCGGCTTATATTCAGGAAATAAGTATGATCTGCTGTTCCCATCTGTCTTAGATGATAACCTGAATGAGAAGATGCTTCAGCTGATATCCCGGTTATGCTGTCTGTACACGGTACTCTTTGCTACAACAAGAGAAATCCCGAAAATAAGAGGCTTAACTGCAGAAGAGAAATGTTCAATACTCACTGAGTATTTACTGTCGGATGCTGTGAAACCATTACTTAGCCCCGATCAAGTGAGCTCTATCATGTCTCCTAACATAATTACATTCCCAGCTAATCTGTACTACATGTCTCGGAAGAGCCTCAATTTGATCAGGGAAAGGGAGGACAGGGATACTATCCTGGCGTTGTTGTTCCCCCAAGAGCCATTATTAGAGTTCCCTTCTGTGCAAGATATTGGTGCTCGAGTGAAAGATCCATTCACCCGACAACCTGCGGCATTTTTGCAAGAGTTAGATTTGAGTGCTCCAGCAAGGTATGACGCATTCACACTTAGTCAGATTCATCCTGAACTCACATCTCCAAATCCGGAGGAAGACTACTTAGTACGATACTTGTTCAGAGGGATAGGGACTGCATCTTCCTCTTGGTATAAGGCATCTCATCTCCTTTCTGTACCCGAGGTAAGATGTGCAAGACACGGGAACTCCTTATACTTAGCTGAAGGGAGCGGAGCCATCATGAGTCTTCTCGAACTGCATGTACCACATGAAACTATCTATTACAATACGCTCTTTTCAAATGAGATGAACCCCCCGCAACGACATTTCGGGCCGACCCCAACTCAGTTTTTGAATTCGGTTGTTTATAGGAATCTACAGGCGGAGGTAACATGCAAAGATGGATTTGTCCAAGAGTTCCGTCCATTATGGAGAGAAAATACAGAGGAAAGTGACCTGACCTCAGATAAAGCAGTGGGGTATATTACATCTGCAGTGCCCTACAGATCTGTATCATTGCTGCATTGTGACATTGAAATTCCTCCAGGGTCCAATCAAAGCTTACTAGATCAACTAGCTATCAATTTATCTCTGATTGCCATGCATTCTGTAAGGGAGGGCGGGGTAGTAATCATCAAAGTGTTGTATGCAATGGGATACTACTTTCATCTACTCATGAACTTGTTTGCTCCGTGTTCCACAAAAGGATATATTCTCTCTAATGGTTATGCATGTCGAGGAGATATGGAGTGTTACCTGGTATTTGTCATGGGTTACCTGGGCGGGCCTACATTTGTACATGAGGTGGTGAGGATGGCAAAAACTCTGGTGCAGCGGCACGGTACGCTCTTGTCTAAATCAGATGAGATCACACTGACCAGGTTATTCACCTCACAGCGGCAGCGTGTGACAGACATCCTATCCAGTCCTTTACCAAGATTAATAAAGTACTTGAGGAAGAATATTGACACTGCGCTGATTGAAGCCGGGGGACAGCCCGTCCGTCCATTCTGTGCGGAGAGTCTGGTGAGCACGCTAGCGAACATAACTCAGATAACCCAGATTATCGCTAGTCACATTGACACAGTTATCCGGTCTGTGATATATATGGAAGCTGAGGGTGATCTCGCTGACACAGTATTTCTATTTACCCCTTACAATCTCTCTACTGACGGGAAAAAGAGGACATCACTTATACAGTGCACGAGACAGATCCTAGAGGTTACAATACTAGGTCTTAGAGTCGAAAATCTCAATAAAATAGGCGATATAATCAGCCTAGTGCTTAAAGGCATGATCTCCATGGAGGACCTTATCCCACTAAGGACATACTTGAAGCATAGTACCTGCCCTAAATATTTGAAGGCTGTCCTAGGTATTACCAAACTCAAAGAAATGTTTACAGACACTTCTGTATTGTACTTGACTCGTGCTCAACAAAAATTCTACATGAAAACTATAGGCAATGCAGTCAAAGGATATTACAGTAACTGTGACTCTTAACGAAAATCACATATTAATAGGCTCCTTTTTTGGCCAATTGTATTCTTGTTGATTTAATCATATTATGTTAGAAAAAAGTTGAACCCTGACTCCTTAGGACTCGAATTCGAACTCAAATAAATGTCTTAAAAAAAGGTTGCGCACAATTATTCTTGAGTGTAGTCTCGTCATTCACCAAATCTTTGTTTGGTGGCCGGCATGGTCCCAGCCTCCTCGCTGGCGCCGGCTGGGCAACATTCCGAGGGGACCGTCCCCTCGGTAATGGCGAATGGGACGTCGACTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTATAT SEQ ID NO:MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS 6; SpikeNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIV proteinNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLE (surfaceGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTglycoprotein)LLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETK (fromCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISN genomeCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIAD MN908947)YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPC (QHD43416.NGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVN 1)FNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITP (1273 aa)GTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT SEQ ID NO:MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS 7: SpikeNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIV proteinNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLE (surfaceGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTglycoprotein),LLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKSouth AfricaCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISN(QIZ15537.1;CVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIAD 1273 aa)YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQGVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT SEQ ID NO:ATGTTCGTGTTCCTGGTCCTGCTGCCACTGGTAAGCTCCCAATGTGTAAACTTAACCACA 8; CodonAGAACCCAGCTCCCACCTGCCTACACCAACAGCTTCACCAGAGGCGTTTATTACCCCGAC OptimizedAAGGTATTCCGGTCTTCTGTTCTGCACTCTACCCAGGACCTGTTTCTGCCCTTTTTCAGCSpike FusionAACGTGACATGGTTCCACGCCATCCACGTGTCTGGCACAAACGGCACCAAGCGGTTTGAT (segmentAATCCTGTGCTCCCTTTCAATGACGGCGTGTACTTCGCCTCTACTGAGAAGAGCAACATCthat went intoATCCGGGGCTGGATCTTTGGCACAACACTGGACTCTAAAACCCAGAGCCTGCTGATCGTG the NDV-AACAACGCCACCAACGTGGTGATTAAGGTGTGCGAGTTCCAGTTCTGCAATGACCCTTTC FLS)CTCGGCGTGTACTACCACAAGAACAACAAAAGTTGGATGGAAAGCGAATTCAGGGTGTAC The productTCAAGCGCCAACAACTGTACCTTCGAGTACGTGAGCCAGCCTTTCCTGATGGACCTAGAAof this codonGGTAAGCAGGGCAATTTCAAGAACCTCAGAGAGTTCGTGTTCAAGAATATTGACGGCTAC optimizedTTCAAAATCTACAGCAAGCACACCCCAATCAACCTGGTGCGGGACCTGCCCCAGGGCTTT gene is SEQAGCGCGCTGGAGCCTCTGGTGGACCTGCCTATCGGCATCAACATCACCCGGTTCCAGACA ID NO: 6CTGCTGGCTCTGCATAGAAGCTACCTGACACCTGGCGACAGTTCTTCTGGCTGGACAGCCGGCGCCGCCGCCTACTACGTGGGCTACCTGCAGCCTAGAACATTCCTGCTGAAATACAACGAGAACGGCACGATCACAGACGCCGTGGACTGCGCCCTGGATCCCCTGTCTGAGACAAAGTGCACCCTGAAGTCTTTCACCGTGGAGAAGGGCATCTACCAGACCTCCAACTTCAGAGTGCAGCCTACCGAATCCATCGTGCGCTTTCCCAACATCACCAACCTGTGCCCCTTCGGCGAGGTCTTTAATGCCACGAGATTCGCCAGCGTGTATGCCTGGAACAGAAAGAGAATCAGCAACTGCGTGGCCGACTACAGCGTGCTGTACAACAGCGCCTCTTTCAGCACATTTAAGTGCTACGGAGTGTCTCCTACCAAACTCAACGATCTGTGCTTCACGAACGTGTATGCCGACAGCTTCGTGATCCGAGGAGATGAGGTGCGGCAGATCGCTCCAGGACAGACAGGCAAGATCGCCGACTACAACTACAAGCTGCCCGACGACTTTACCGGCTGCGTGATCGCTTGGAACAGCAATAACCTGGACTCAAAGGTTGGAGGAAACTACAACTACCTGTACAGACTGTTCAGAAAGTCCAACCTGAAGCCCTTCGAGAGAGACATCTCTACAGAAATCTACCAGGCCGGCAGCACCCCATGTAACGGCGTGGAAGGCTTCAACTGCTACTTCCCTCTGCAGTCTTATGGCTTCCAGCCCACAAACGGAGTGGGCTATCAGCCTTACCGCGTGGTTGTCCTGAGCTTTGAGCTGCTGCATGCCCCTGCTACGGTGTGTGGACCTAAGAAGTCCACCAACCTGGTGAAGAACAAGTGTGTGAACTTCAACTTCAACGGCCTGACCGGCACCGGGGTGCTGACAGAGTCTAACAAGAAATTCCTGCCATTCCAGCAATTCGGCCGGGACATCGCCGACACCACCGACGCCGTGCGGGATCCTCAGACCCTCGAAATCCTGGACATCACCCCCTGTAGCTTCGGCGGCGTGAGCGTGATCACCCCTGGCACAAACACCAGCAATCAAGTGGCTGTCCTGTACCAGGATGTCAATTGCACAGAAGTGCCTGTGGCCATCCACGCCGATCAGCTGACCCCCACCTGGCGGGTGTACTCGACAGGAAGCAACGTGTTTCAAACAAGAGCCGGCTGCCTGATCGGGGCCGAGCACGTGAACAATTCCTACGAGTGCGACATCCCCATCGGCGCCGGCATCTGTGCCTCTTACCAGACACAGACCAATTCCCCTCGTAGAGCCAGATCCGTGGCCAGCCAGAGCATCATCGCCTACACCATGAGCCTGGGCGCCGAAAACAGCGTTGCATATTCCAACAACAGCATCGCCATCCCTACCAACTTCACCATCAGCGTGACCACAGAAATCCTGCCTGTGTCCATGACCAAGACAAGCGTTGATTGCACCATGTACATCTGCGGCGATAGCACAGAGTGCAGCAATCTGCTGCTGCAGTACGGTAGCTTCTGCACCCAGCTGAATAGAGCCCTGACCGGCATCGCTGTGGAACAGGACAAAAACACCCAGGAGGTCTTCGCCCAGGTGAAGCAAATCTACAAGACCCCTCCAATCAAGGACTTCGGAGGCTTTAACTTTAGCCAGATCCTGCCTGATCCCTCCAAGCCTAGCAAACGGAGTTTCATCGAGGACCTGCTCTTCAACAAGGTGACCCTGGCTGACGCCGGCTTCATTAAGCAGTACGGCGATTGCCTCGGCGACATCGCTGCAAGAGACCTGATCTGCGCCCAGAAGTTCAACGGCCTGACCGTGCTGCCTCCTCTCCTGACAGACGAGATGATCGCCCAGTACACCTCTGCCCTTCTGGCTGGCACCATCACCAGCGGATGGACCTTTGGAGCCGGAGCCGCCCTGCAGATCCCTTTCGCTATGCAGATGGCCTACAGATTCAACGGGATCGGAGTGACCCAAAACGTGCTGTATGAAAACCAGAAACTGATCGCCAATCAGTTTAACAGCGCCATCGGCAAAATCCAGGATAGCCTGTCCAGCACCGCCAGCGCCCTCGGCAAGCTGCAAGATGTGGTGAATCAAAATGCCCAAGCCCTGAACACACTGGTGAAGCAGCTGAGCAGCAACTTCGGCGCCATCAGCAGCGTGCTGAACGACATCCTGAGCAGACTGGACAAGGTGGAAGCCGAGGTGCAGATCGACAGACTGATCACAGGCAGACTGCAGTCCCTGCAGACCTACGTGACCCAGCAGTTGATTAGAGCCGCTGAGATTAGAGCCAGTGCCAACCTGGCTGCCACAAAGATGTCAGAATGCGTGCTGGGCCAGAGCAAGAGAGTGGACTTCTGCGGCAAAGGCTACCACCTGATGAGCTTTCCTCAGTCTGCACCCCACGGCGTGGTGTTTCTCCACGTGACATACGTGCCCGCGCAAGAAAAGAACTTTACAACCGCCCCAGCGATCTGCCACGACGGCAAGGCCCACTTCCCTCGGGAGGGTGTGTTCGTGAGCAATGGAACACACTGGTTCGTCACCCAGCGGAACTTCTACGAGCCTCAGATCATTACCACCGACAACACCTTCGTGAGCGGCAACTGTGACGTCGTTATCGGCATCGTGAACAATACCGTGTACGACCCCCTGCAGCCTGAGCTGGATAGCTTCAAAGAGGAACTGGACAAGTACTTCAAGAACCACACAAGCCCCGACGTGGACCTAGGCGACATCTCTGGAATCAACGCCAGCGTGGTGAACATCCAAAAGGAAATCGACAGACTGAACGAGGTGGCCAAGAATCTGAATGAAAGCCTGATCGATCTGCAGGAGCTGGGCAAGTACGAGCAGTACATCAAATGGCCTTGGTACATCTGGCTGGGCTTCATCGCTGGTCTGATCGCTATCGTGATGGTGACCATTATGCTGTGCTGCATGACCTCCTGCTGCTCTTGCCTGAAGGGCTGTTGTTCTTGCGGCTCTTGCTGCAAGTTCGACGAGGATGACTCTGAACCTGTTCTGAAGGGCGTGAAGCTGCACTACACCTGATaa SEQ ID NO:TAATACGACTCACTATAGGGACCAAACAGAGAATCCGTGAGTTACGATAAAAGGCGAAGG 9; ChimericAGCAATTGAAGTCGCACGGGTAGAAGGTGTGAATCTCGAGTGCGAGCCCGAAGCACAAAC NDV withTCGAGAAAGCCTTCTGCCAACATGTCTTCCGTATTTGATGAGTACGAACAGCTCCTCGCG APMV-5 FGCTCAGACTCGCCCCAATGGAGCTCATGGAGGGGGAGAAAAAGGGAGTACCTTAAAAGTA and HNGACGTCCCGGTATTCACTCTTAACAGTGATGACCCAGAAGATAGATGGAGCTTTGTGGTA without GFPTTCTGCCTCCGGATTGCTGTTAGCGAAGATGCCAACAAACCACTCAGGCAAGGTGCTCTCATATCTCTTTTATGCTCCCACTCACAGGTAATGAGGAACCATGTTGCCATTGCAGGGAAACAGAATGAAGCCACATTGGCCGTGCTTGAGATTGATGGCTTTGCCAACGGCACGCCCCAGTTCAACAATAGGAGTGGAGTGTCTGAAGAGAGAGCACAGAGATTTGCGATGATAGCAGGATCTCTCCCTCGGGCATGCAGCAACGGAACCCCGTTCGTCACAGCCGGGGCAGAAGATGATGCACCAGAAGACATCACCGATACCCTGGAGAGGATCCTCTCTATCCAGGCTCAAGTATGGGTCACAGTAGCAAAAGCCATGACTGCGTATGAGACTGCAGATGAGTCGGAAACAAGGCGAATCAATAAGTATATGCAGCAAGGCAGGGTCCAAAAGAAATACATCCTCTACCCCGTATGCAGGAGCACAATCCAACTCACGATCAGACAGTCTCTTGCAGTCCGCATCTTTTTGGTTAGCGAGCTCAAGAGAGGCCGCAACACGGCAGGTGGTACCTCTACTTATTATAACCTGGTAGGGGACGTAGACTCATACATCAGGAATACCGGGCTTACTGCATTCTTCTTGACACTCAAGTACGGAATCAACACCAAGACATCAGCCCTTGCACTTAGTAGCCTCTCAGGCGACATCCAGAAGATGAAGCAGCTCATGCGTTTGTATCGGATGAAAGGAGATAATGCGCCGTACATGACATTACTTGGTGATAGTGACCAGATGAGCTTTGCGCCTGCCGAGTATGCACAACTTTACTCCTTTGCCATGGGTATGGCATCAGTCCTAGATAAAGGTACTGGGAAATACCAATTTGCCAGGGACTTTATGAGCACATCATTCTGGAGACTTGGAGTAGAGTACGCTCAGGCTCAGGGAAGTAGCATTAACGAGGATATGGCTGCCGAGCTAAAGCTAACCCCAGCAGCAATGAAGGGCCTGGCAGCTGCTGCCCAACGGGTCTCCGACGATACCAGCAGCATATACATGCCTACTCAACAAGTCGGAGTCCTCACTGGGCTTAGCGAGGGGGGGTCCCAAGCTCTACAAGGCGGATCGAATAGATCGCAAGGGCAACCAGAAGCCGGGGATGGGGAGACCCAATTCCTGGATCTGATGAGAGCGGTAGCAAATAGCATGAGGGAGGCGCCAAACTCTGCACAGGGCACTCCCCAATCGGGGCCTCCCCCAACTCCTGGGCCATCCCAAGATAACGACACCGACTGGGGGTATTGATGGACAAAACCCAGCCTGCTTCCACAAAAACATCCCAATGCCCTCACCCGTAGTCGACCCCTCGATTTGCGGCTCTATATGACCACACCCTCAAACAAACATCCCCCTCTTTCCTCCCTCCCCCTGCTGTACAACTCCGCACGCCCTAGATACCACAGGCACAATGCGGCTCACTAACAATCAAAACAGAGCCGAGGGAATTAGAAAAAAGTACGGGTAGAAGAGGGATATTCAGAGATCAGGGCAAGTCTCCCGAGTCTCTGCTCTCTCCTCTACCTGATAGACCAGGACAAACATGGCCACCTTTACAGATGCAGAGATCGACGAGCTATTTGAGACAAGTGGAACTGTCATTGACAACATAATTACAGCCCAGGGTAAACCAGCAGAGACTGTTGGAAGGAGTGCAATCCCACAAGGCAAGACCAAGGTGCTGAGCGCAGCATGGGAGAAGCATGGGAGCATCCAGCCACCGGCCAGTCAAGACAACCCCGATCGACAGGACAGATCTGACAAACAACCATCCACACCCGAGCAAACGACCCCGCATGACAGCCCGCCGGCCACATCCGCCGACCAGCCCCCCACCCAGGCCACAGACGAAGCCGTCGACACACAGTTCAGGACCGGAGCAAGCAACTCTCTGCTGTTGATGCTTGACAAGCTCAGCAATAAATCGTCCAATGCTAAAAAGGGCCCATGGTCGAGCCCCCAAGAGGGGAATCACCAACGTCCGACTCAACAGCAGGGGAGTCAACCCAGTCGCGGAAACAGTCAGGAAAGACCGCAGAACCAAGTCAAGGCCGCCCCTGGAAACCAGGGCACAGACGTGAACACAGCATATCATGGACAATGGGAGGAGTCACAACTATCAGCTGGTGCAACCCCTCATGCTCTCCGATCAAGGCAGAGCCAAGACAATACCCTTGTATCTGCGGATCATGTCCAGCCACCTGTAGACTTTGTGCAAGCGATGATGTCTATGATGGAGGCGATATCACAGAGAGTAAGTAAGGTTGACTATCAGCTAGATCTTGTCTTGAAACAGACATCCTCCATCCCTATGATGCGGTCCGAAATCCAACAGCTGAAAACATCTGTTGCAGTCATGGAAGCCAACTTGGGAATGATGAAGATTCTGGATCCCGGTTGTGCCAACATTTCATCTCTGAGTGATCTACGGGCAGTTGCCCGATCTCACCCGGTTTTAGTTTCAGGCCCTGGAGACCCCTCTCCCTATGTGACACAAGGAGGCGAAATGGCACTTAATAAACTTTCGCAACCAGTGCCACATCCATCTGAATTGATTAAACCCGCCACTGCATGCGGGCCTGATATAGGAGTGGAAAAGGACACTGTCCGTGCATTGATCATGTCACGCCCAATGCACCCGAGTTCTTCAGCCAAGCTCCTAAGCAAGTTAGATGCAGCCGGGTCGATCGAGGAAATCAGGAAAATCAAGCGCCTTGCTCTAAATGGCTAATTACTACTGCCACACGTAGCGGGTCCCTGTCCACTCGGCATCACACGGAATCTGCACCGAGTTCCCCCtctagaaaacgcgtACCCAAGGTCCAACTCTCCAAGCGGCAATCCTCTCTCGCTTCCTCAGCCCCACTGAATGGTCGCGTAACCGTAATTAATCTAGCTACATTTAAGATTAAGAAAAAATACGGGTAGAATTGGAGTGCCCCAATTGTGCCAAGATGGACTCATCTAGGACAATTGGGCTGTACTTTGATTCTGCCCATTCTTCTAGCAACCTGTTAGCATTTCCGATCGTCCTACAAGGCACAGGAGATGGGAAGAAGCAAATCGCCCCGCAATATAGGATCCAGCGCCTTGACTTGTGGACTGATAGTAAGGAGGACTCAGTATTCATCACCACCTATGGATTCATCTTTCAAGTTGGGAATGAAGAAGCCACTGTCGGCATGATCGATGATAAACCCAAGCGCGAGTTACTTTCCGCTGCGATGCTCTGCCTAGGAAGCGTCCCAAATACCGGAGACCTTATTGAGCTGGCAAGGGCCTGTCTCACTATGATAGTCACATGCAAGAAGAGTGCAACTAATACTGAGAGAATGGTTTTGTCAGTAGTGCAGGCACCCCAAGTGCTGCAAAGCTGTAGGGTTGTGGCAAACAAATACTCATCAGTGAATGCAGTCAAGCACGTGAAAGCGCCAGAGAAGATTCCCGGGAGTGGAACCCTAGAATACAAGGTGAACTTTGTCTCCTTGACTGTGGTACCGAAGAAGGATGTCTACAAGATCCCAGCTGCAGTATTGAAGGTTTCTGGCTCGAGTCTGTACAATCTTGCGCTCAATGTCACTATTAATGTGGAGGTAGACCCGAGGAGTCCTTTGGTTAAATCTTTGTCTAAGTCTGACAGCGGATACTATGCTAACCTCTTCTTGCATATTGGACTTATGACCACCGTAGATAGGAAGGGGAAGAAAGTGACATTTGACAAGCTGGAAAAGAAAATAAGGAGCCTTGATCTATCTGTCGGGCTCAGTGATGTGCTCGGGCCTTCCGTGTTGGTAAAAGCAAGAGGTGCACGGACTAAGCTTTTGGCACCTTTCTTCTCTAGCAGTGGGACAGCCTGCTATCCCATAGCAAATGCTTCTCCTCAGGTGGCCAAGATACTCTGGAGTCAAACCGCGTGCCTGCGGAGCGTTAAAATCATTATCCAAGCAGGTACCCAACGCGCTGTCGCAGTGACCGCCGACCACGAGGTTACCTCTACTAAGCTGGAGAAGGGGCACACCCTTGCCAAATACAATCCTTTTAAGAAATAAGCTGCGTCTCTGAGATTGCGCTCCGCCCACTCACCCAGATCATCATGACACAAAAAACTAATCTGTCTTGATTATTTACAGTTAGTTTACCTGTCTATCAAGTTAGAAAAAACACGGGTAGAAGATTCTGGATCCCGGTTGGCGCCCTCCAGGTGCAAGttaattaaATGTTACAACTTCCCTTGACCATTCTTCTTAGCATTCTTAGTGCTCACCAGTCGCTTTGTCTAGACAACAGTAAGCTCATTCATGCAGGAATCATGAGTACTACTGAGAGAGAAGTTAATGTTTATGCACAATCTATTACTGGGTCAATAGTGGTGAGATTGATTCCAAATATCCCAAGTAACCATAAATCTTGTGCAACTAGCCAAATCAAATTATACAATGACACGTTAACAAGATTGTTGACCCCAATTAAAGCTAATCTAGAAGGACTTATTAGTGCTGTTTCTCAGGACCAATCGCAGAATTCTGGGAAGAGAAAGAAGCGTTTTGTAGGCGCAGTAATTGGAGCAGCTGCCCTTGGTTTGGCAACTGCTGCACAGGTGACTGCCACTGTAGCATTAAATCAAGCGCAAGAAAACGCTCGGAATATCCTAAGGCTTAAAAACTCGATTCAGAAGACAAACGAGGCGGTGATGGAACTTAAAGATGCTGTGGGCCAAACAGCAGTAGCTATTGACAAAACTCAGGCCTTCATAAATAATCAAATCTTGCCTGCAATTTCAAATCTCTCATGTGAGGTCCTAGGGAATAAAATTGGGGTCCAATTATCTTTGTACCTTACTGAATTAACAACAGTATTCGGCAACCAACTGACAAACCCAGCCCTTACCACACTGTCATTACAAGCCTTGTACAATCTTTGTGGAGATGACTTCAATTACTTAATCAACCTATTAAATGCAAAAAATCGTAACTTAGCCTCACTTTATGAAGCAAACCTAATTCAGGGGAGAATTACTCAATATGACTCAATGAATCAGTTATTAATTATTCAGGTACAAATACCAAGCATCTCCACAGTGTCAGGAATGAGGGTCACAGAATTGTTCACACTTAGTGTTGACACACCTATAGGAGAGGGAAAGGCCCTAGTACCAAAATATGTCCTATCCTCAGGGAGAATAATGGAAGAGGTTGACCTAAGCAGTTGCGCTATAACATCAACATCAGTTTTCTGTTCCTCTATCATCTCTAGACCCCTTCCACTTGAAACAATAAATTGCCTGAATGGGAATGTTACACAGTGTCAATTTACCGCCAACACAGGAACCCTTGAATCGAGATACGCTGTTATAGGAGGATTGGTGATTGCTAACTGTAAGGCTATAGTATGCAGGTGCCTAAATCCACCAGGTGTCATTGCGCAAAATCTTGGCTTACCAATTACAATCATCTCATCCAATACTTGTCAGCGAATTAATTTAGAACAAATCACTTTGTCTCTTGGGAACAGCATATTATCTACATACAGTGCCAATTTATCCCAAGTTGAGATGAATTTAGCTCCATCAAATCCTCTGGATATCTCAGTTGAATTGAATCGAGTCAACACCAGTCTCTCTAAAGTGGAATCTCTAATAAAAGAAAGCAATAGTATCCTGGACTCAGTAAACCCTCAAATTTTAAATGTCAAGACACTCATTACgTATATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTGATTCTAGCATGCTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTTATTATGGCTTGGGAATAATACaCTcGATCAGATGAGAGCCACTACAAAAATGTGAACACAGATGAGGAACGAAGGTTTCCCTAATAGTAATTTGTGTGAAAGTTCTGGTAGTCTGTCAGTTCAGAGAGTTAAGAAAAAACTACCGGTTGTAGATGACCAAAGGACGATATACGGGTAGAACGGTAAGAGAGGCCGCCCCTCAATTGCGAGCCAGGCTTCACAACCTCCGTTCTACCGCTTCACCGACAACAGTCCTCAATCATGGACCGCGCCGTTAGCCAAGTTGCGTTAGAGAATGATGAAAGAGAGGCAAAAAATACATGGCGCTTGATATTCCGGATTGCAATCTTATTCTTAACAGTAGTGACCTTGGCTATATCTGTAGCCTCCCTTTTATATAGCATGGGGGCTAGCACACCTTCCACTCTGATCAGCCTAAATAACTCAATTATCACAAGCAGCAATGGTCTCAAAAAGGAAATCCTGAACCAGAACATAAAAGAGGACCTCATATATAGAGAAGTTGCTATAAATATACCTTTAACATTAGATAGGGTTACTGTTGAGGTAGGGACTGCAGTAAACCAGATTACTGATGCACTCAGGCAACTCCAGTCAGTTAATGGATCTGCTGCATTCGCCTCATCAAACTCTCCTGATTATAGTGGGGGAATAGAACACCTGATTTTCCAAAGGAATACGCTTATTAATCGCTCAGTGAGTGTCTCAGATTTAATAGAACACCCCAGTTTCATACCAACTCCTACTACACAGCATGGTTGTACCAGAATCCCCACATTCCACCTAGGAACTCGCCACTGGTGCTATAGTCACAATATAATAGGTCAGGGATGTGCTGATTCTAGAGCTAGTGTGATGTATATTTCAATGGGAGCACTGGGTGTCAGTTCATTGGGAACCCCGACCTTCACAACATCTGCTGCATCAATATTATCTGATAGCCTCAATCGGAAGAGTTGCAGTATAGTAGCAACAACTGAGGGTTGTGACGTACTCTGCAGTATAGTTACACAAACAGAAGACCAAGATTATGCTGATCACACTCCTACTCCAATGATACATGGTAGATTATGGTTTAATGGCACATACACAGAGAGATCCTTATCCCAGAGTTTATTCCTTGGAACATGGGCTGCGCAATATCCGGCTGTAGGATCTGGTATAATGACACCTGGGCGAGTTATATTCCCTTTCTATGGAGGTGTGATCCCTAACTCTCCTCTCTTCTTGGATCTCGAAAGATTCGCTTTATTCACACATAATGGAGACTTAGAATGCATGAACTTAACACAATATCAGAAAGAAGCAATTTACTCTGCATATAAGCCTCCCAAGATTAGAGGATCACTGTGGGCACAAGGCTTCATAGTATGTTCAGTAGGAGACATGGGGAATTGCTCTCTTAAAGTGATCAATACAAGCACAGTTATGATGGGTGCAGAAGGTCGGCTACAATTAGTTGGGGACTCCGTTATGTACTATCAGAGATCATCATCCTGGTGGCCTGTAGGAATTCTTTATCGGTTGAGTCTTGTAGACATCATCGCCGGAGATATACAGGTCGTCATAAACAGTGAACCACTCCCTCTGAGCAAGTTCCCGCGGCCAACCTGGACTCCAGGAGTGTGTCAAAAACCAAATGTATGCCCTGCAGTTTGTGTAACTGGGGTCTATCAAGACCTTTGGGCAATTTCCGCAGGGGAGACACTATCTGAAATGACATTCTTTGGAGGATATTTAGAGGCATCCACCCAACGAAAAGATCCATGGATAGGCGTTGCTAATCAATATAGTTGGTTCATGAGAAGAAGATTATTCAAGACAAGCACTGAAGCTGCATATTCGTCATCAACGTGTTTTAGGAACACTAGACTGGATCGAAATTTCTGCCTATTAGTCTTTGAATTAACTGATAACTTACTTGGAGACTGGAGAATTGTCCCCCTCTTATTTGAATTAACCATCGTATAAggcgcgccTTGAGTCAATTATAAAGGAGTTGGAAAGATGGCATTGTATCACCTATCTTCTGCGACATCAAGAATCAAACCGAATGCCGGCGCGTGCTCGAATTCCATGTTGCCAGTTGACCACAATCAGCCAGTGCTCATGCGATCAGATTAAGCCTTGTCATTAATCTCTTGATTAAGAAAAAATGTAAGTGGCAATGAGATACAAGGCAAAACAGCTCATGGTAAATAATACGGGTAGGACATGGCGAGCTCCGGTCCTGAAAGGGCAGAGCATCAGATTATCCTACCAGAGCCACACCTGTCTTCACCATTGGTCAAGCACAAACTACTCTATTACTGGAAATTAACTGGGCTACCGCTTCCTGATGAATGTGACTTCGACCACCTCATTCTCAGCCGACAATGGAAAAAAATACTTGAATCGGCCTCTCCTGATACTGAGAGAATGATAAAACTCGGAAGGGCAGTACACCAAACTCTTAACCACAATTCCAGAATAACCGGAGTGCTCCACCCCAGGTGTTTAGAACAACTGGCTAATATTGAGGTCCCAGATTCAACCAACAAATTTCGGAAGATTGAGAAGAAGATCCAAATTCACAACACGAGATATGGAGAACTGTTCACAAGGCTGTGTACGCATATAGAGAAGAAACTGCTGGGGTCATCTTGGTCTAACAATGTCCCCCGGTCAGAGGAGTTCAGCAGCATTCGTACGGATCCGGCATTCTGGTTTCACTCAAAATGGTCCACAGCCAAGTTTGCATGGCTCCATATAAAACAGATCCAGAGGCATCTGATGGTGGCAGCTAAGACAAGGTCTGCGGCCAACAAATTGGTGATGCTAACCCATAAGGTAGGCCAAGTCTTTGTCACTCCTGAACTTGTCGTTGTGACGCATACGAATGAGAACAAGTTCACATGTCTTACCCAGGAACTTGTATTGATGTATGCAGATATGATGGAGGGCAGAGATATGGTCAACATAATATCAACCACGGCGGTGCATCTCAGAAGCTTATCAGAGAAAATTGATGACATTTTGCGGTTAATAGACGCTCTGGCAAAAGACTTGGGTAATCAAGTCTACGATGTTGTATCACTAATGGAGGGATTTGCATACGGAGCTGTCCAGCTACTCGAGCCGTCAGGTACATTTGCAGGAGATTTCTTCGCATTCAACCTGCAGGAGCTTAAAGACATTCTAATTGGCCTCCTCCCCAATGATATAGCAGAATCCGTGACTCATGCAATCGCTACTGTATTCTCTGGTTTAGAACAGAATCAAGCAGCTGAGATGTTGTGTCTGTTGCGTCTGTGGGGTCACCCACTGCTTGAGTCCCGTATTGCAGCAAAGGCAGTCAGGAGCCAAATGTGCGCACCGAAAATGGTAGACTTTGATATGATCCTTCAGGTACTGTCTTTCTTCAAGGGAACAATCATCAACGGGTACAGAAAGAAGAATGCAGGTGTGTGGCCGCGAGTCAAAGTGGATACAATATATGGGAAGGTCATTGGGCAACTACATGCAGATTCAGCAGAGATTTCACACGATATCATGTTGAGAGAGTATAAGAGTTTATCTGCACTTGAATTTGAGCCATGTATAGAATATGACCCTGTCACCAACCTGAGCATGTTCCTAAAAGACAAGGCAATCGCACACCCCAACGATAATTGGCTTGCCTCGTTTAGGCGGAACCTTCTCTCCGAAGACCAGAAGAAACATGTAAAAGAAGCAACTTCGACTAATCGCCTCTTGATAGAGTTTTTAGAGTCAAATGATTTTGATCCATATAAAGAGATGGAATATCTGACGACCCTTGAGTACCTTAGAGATGACAATGTGGCAGTATCATACTCGCTCAAGGAGAAGGAAGTGAAAGTTAATGGACGGATCTTCGCTAAGCTGACAAAGAAGTTAAGGAACTGTCAGGTGATGGCGGAAGGGATCCTAGCCGATCAGATTGCACCTTTCTTTCAGGGAAATGGAGTCATTCAGGATAGCATATCCTTGACCAAGAGTATGCTAGCGATGAGTCAACTGTCTTTTAACAGCAATAAGAAACGTATCACTGACTGTAAAGAAAGAGTATCTTCAAACCGCAATCATGATCCGAAAAGCAAGAACCGTCGGAGAGTTGCAACCTTCATAACAACTGACCTGCAAAAGTACTGTCTTAATTGGAGATATCAGACAATCAAATTGTTCGCTCATGCCATCAATCAGTTGATGGGCCTACCTCACTTCTTCGAATGGATTCACCTAAGACTGATGGACACTACGATGTTCGTAGGAGACCCTTTCAATCCTCCAAGTGACCCTACTGACTGTGACCTCTCAAGAGTCCCTAATGATGACATATATATTGTCAGTGCCAGAGGGGGTATCGAAGGATTATGCCAGAAGCTATGGACAATGATCTCAATTGCTGCAATCCAACTTGCTGCAGCTAGATCGCATTGTCGTGTTGCCTGTATGGTACAGGGTGATAATCAAGTAATAGCAGTAACGAGAGAGGTAAGATCAGACGACTCTCCGGAGATGGTGTTGACACAGTTGCATCAAGCCAGTGATAATTTCTTCAAGGAATTAATTCATGTCAATCATTTGATTGGCCATAATTTGAAGGATCGTGAAACCATCAGGTCAGACACATTCTTCATATACAGCAAACGAATCTTCAAAGATGGAGCAATCCTCAGTCAAGTCCTCAAAAATTCATCTAAATTAGTGCTAGTGTCAGGTGATCTCAGTGAAAACACCGTAATGTCCTGTGCCAACATTGCCTCTACTGTAGCACGGCTATGCGAGAACGGGCTTCCCAAAGACTTCTGTTACTATTTAAACTATATAATGAGTTGTGTGCAGACATACTTTGACTCTGAGTTCTCCATCACCAACAATTCGCACCCCGATCTTAATCAGTCGTGGATTGAGGACATCTCTTTTGTGCACTCATATGTTCTGACTCCTGCCCAATTAGGGGGACTGAGTAACCTTCAATACTCAAGGCTCTACACTAGAAATATCGGTGACCCGGGGACTACTGCTTTTGCAGAGATCAAGCGACTAGAAGCAGTGGGATTACTGAGTCCTAACATTATGACTAATATCTTAACTAGGCCGCCTGGGAATGGAGATTGGGCCAGTCTGTGCAACGACCCATACTCTTTCAATTTTGAGACTGTTGCAAGCCCAAATATTGTTCTTAAGAAACATACGCAAAGAGTCCTATTTGAAACTTGTTCAAATCCCTTATTGTCTGGAGTGCACACAGAGGATAATGAGGCAGAAGAGAAGGCATTGGCTGAATTCTTGCTTAATCAAGAGGTGATTCATCCCCGCGTTGCGCATGCCATCATGGAGGCAAGCTCTGTAGGTAGGAGAAAGCAAATTCAAGGGCTTGTTGACACAACAAACACCGTAATTAAGATTGCGCTTACTAGGAGGCCATTAGGCATCAAGAGGCTGATGCGGATAGTCAATTATTCTAGCATGCATGCAATGCTGTTTAGAGACGATGTTTTTTCCTCCAGTAGATCCAACCACCCCTTAGTCTCTTCTAATATGTGTTCTCTGACACTGGCAGACTATGCACGGAATAGAAGCTGGTCACCTTTGACGGGAGGCAGGAAAATACTGGGTGTATCTAATCCTGATACGATAGAACTCGTAGAGGGTGAGATTCTTAGTGTAAGCGGAGGGTGTACAAGATGTGACAGCGGAGATGAACAATTTACTTGGTTCCATCTTCCAAGCAATATAGAATTGACCGATGACACCAGCAAGAATCCTCCGATGAGGGTACCATATCTCGGGTCAAAGACACAGGAGAGGAGAGCTGCCTCACTTGCAAAAATAGCTCATATGTCGCCACATGTAAAGGCTGCCCTAAGGGCATCATCCGTGTTGATCTGGGCTTATGGGGATAATGAAGTAAATTGGACTGCTGCTCTTACGATTGCAAAATCTCGGTGTAATGTAAACTTAGAGTATCTTCGGTTACTGTCCCCTTTACCCACGGCTGGGAATCTTCAACATAGACTAGATGATGGTATAACTCAGATGACATTCACCCCTGCATCTCTCTACAGGgtgtcaccttacattcacatatccaatgattctcaaaggctgttcactgaagaaggagtcaaagaggggaatgtggtttaccaacagatcATGCTCTTGGGTTTATCTCTAATCGAATCGATCTTTCCAATGACAACAACGAGGACATATGATGAGATCACACTGCACCTACATAGTAAATTTAGTTGCTGTATCAGAGAAGCACCTGTTGCGGTTCCTTTCGAGCTACTTGGGGTGGTACCGGAACTGAGGACAGTGACCTCAAATAAGTTTATGTATGATCCTAGCCCTGTATCGGAGGGAGACTTTGCGAGACTTGACTTAGCTATCTTCAAGAGTTATGAGCTTAATCTGGAGTCATATCCCACGATAGAGCTAATGAACATTCTTTCAATATCCAGCGGGAAGTTGATTGGCCAGTCTGTGGTTTCTTATGATGAAGATACCTCCATAAAGAATGACGCCATAATAGTGTATGACAATACCCGAAATTGGATCAGTGAAGCTCAGAATTCAGATGTGGTCCGCCTATTTGAATATGCAGCACTTGAAGTGCTCCTCGACTGTTCTTACCAACTCTATTACCTGAGAGTAAGAGGCCTAGACAATATTGTCTTATATATGGGTGATTTATACAAGAATATGCCAGGAATTCTACTTTCCAACATTGCAGCTACAATATCTCATCCCGTCATTCATTCAAGGTTACATGCAGTGGGCCTGGTCAACCATGACGGATCACACCAACTTGCAGATACGGATTTTATCGAAATGTCTGCAAAACTATTAGTATCTTGCACCCGACGTGTGATCTCCGGCTTATATTCAGGAAATAAGTATGATCTGCTGTTCCCATCTGTCTTAGATGATAACCTGAATGAGAAGATGCTTCAGCTGATATCCCGGTTATGCTGTCTGTACACGGTACTCTTTGCTACAACAAGAGAAATCCCGAAAATAAGAGGCTTAACTGCAGAAGAGAAATGTTCAATACTCACTGAGTATTTACTGTCGGATGCTGTGAAACCATTACTTAGCCCCGATCAAGTGAGCTCTATCATGTCTCCTAACATAATTACATTCCCAGCTAATCTGTACTACATGTCTCGGAAGAGCCTCAATTTGATCAGGGAAAGGGAGGACAGGGATACTATCCTGGCGTTGTTGTTCCCCCAAGAGCCATTATTAGAGTTCCCTTCTGTGCAAGATATTGGTGCTCGAGTGAAAGATCCATTCACCCGACAACCTGCGGCATTTTTGCAAGAGTTAGATTTGAGTGCTCCAGCAAGGTATGACGCATTCACACTTAGTCAGATTCATCCTGAACTCACATCTCCAAATCCGGAGGAAGACTACTTAGTACGATACTTGTTCAGAGGGATAGGGACTGCATCTTCCTCTTGGTATAAGGCATCTCATCTCCTTTCTGTACCCGAGGTAAGATGTGCAAGACACGGGAACTCCTTATACTTAGCTGAAGGGAGCGGAGCCATCATGAGTCTTCTCGAACTGCATGTACCACATGAAACTATCTATTACAATACGCTCTTTTCAAATGAGATGAACCCCCCGCAACGACATTTCGGGCCGACCCCAACTCAGTTTTTGAATTCGGTTGTTTATAGGAATCTACAGGCGGAGGTAACATGCAAAGATGGATTTGTCCAAGAGTTCCGTCCATTATGGAGAGAAAATACAGAGGAAAGTGACCTGACCTCAGATAAAGCAGTGGGGTATATTACATCTGCAGTGCCCTACAGATCTGTATCATTGCTGCATTGTGACATTGAAATTCCTCCAGGGTCCAATCAAAGCTTACTAGATCAACTAGCTATCAATTTATCTCTGATTGCCATGCATTCTGTAAGGGAGGGCGGGGTAGTAATCATCAAAGTGTTGTATGCAATGGGATACTACTTTCATCTACTCATGAACTTGTTTGCTCCGTGTTCCACAAAAGGATATATTCTCTCTAATGGTTATGCATGTCGAGGAGATATGGAGTGTTACCTGGTATTTGTCATGGGTTACCTGGGCGGGCCTACATTTGTACATGAGGTGGTGAGGATGGCAAAAACTCTGGTGCAGCGGCACGGTACGCTCTTGTCTAAATCAGATGAGATCACACTGACCAGGTTATTCACCTCACAGCGGCAGCGTGTGACAGACATCCTATCCAGTCCTTTACCAAGATTAATAAAGTACTTGAGGAAGAATATTGACACTGCGCTGATTGAAGCCGGGGGACAGCCCGTCCGTCCATTCTGTGCGGAGAGTCTGGTGAGCACGCTAGCGAACATAACTCAGATAACCCAGATTATCGCTAGTCACATTGACACAGTTATCCGGTCTGTGATATATATGGAAGCTGAGGGTGATCTCGCTGACACAGTATTTCTATTTACCCCTTACAATCTCTCTACTGACGGGAAAAAGAGGACATCACTTATACAGTGCACGAGACAGATCCTAGAGGTTACAATACTAGGTCTTAGAGTCGAAAATCTCAATAAAATAGGCGATATAATCAGCCTAGTGCTTAAAGGCATGATCTCCATGGAGGACCTTATCCCACTAAGGACATACTTGAAGCATAGTACCTGCCCTAAATATTTGAAGGCTGTCCTAGGTATTACCAAACTCAAAGAAATGTTTACAGACACTTCTGTATTGTACTTGACTCGTGCTCAACAAAAATTCTACATGAAAACTATAGGCAATGCAGTCAAAGGATATTACAGTAACTGTGACTCTTAACGAAAATCACATATTAATAGGCTCCTTTTTTGGCCAATTGTATTCTTGTTGATTTAATCATATTATGTTAGAAAAAAGTTGAACCCTGACTCCTTAGGACTCGAATTCGAACTCAAATAAATGTCTTAAAAAAAGGTTGCGCACAATTATTCTTGAGTGTAGTCTCGTCATTCACCAAATCTTTGTTTGGTGGCCGGCATGGTCCCAGCCTCCTCGCTGGCGCCGGCTGGGCAACATTCCGAGGGGACCGTCCCCTCGGTAATGGCGAATGGGACGTCGACTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTATAT SEQ ID NO:TAATACGACTCACTATAGGGACCAAACAGAGAATCCGTGAGTTACGATAAAAGGCGAAGG 10; NDVAGCAATTGAAGTCGCACGGGTAGAAGGTGTGAATCTCGAGTGCGAGCCCGAAGCACAAAC vectorTCGAGAAAGCCTTCTGCCAACATGTCTTCCGTATTTGATGAGTACGAACAGCTCCTCGCG lentogenicGCTCAGACTCGCCCCAATGGAGCTCATGGAGGGGGAGAAAAAGGGAGTACCTTAAAAGTA without GFPGACGTCCCGGTATTCACTCTTAACAGTGATGACCCAGAAGATAGATGGAGCTTTGTGGTATTCTGCCTCCGGATTGCTGTTAGCGAAGATGCCAACAAACCACTCAGGCAAGGTGCTCTCATATCTCTTTTATGCTCCCACTCACAGGTAATGAGGAACCATGTTGCCATTGCAGGGAAACAGAATGAAGCCACATTGGCCGTGCTTGAGATTGATGGCTTTGCCAACGGCACGCCCCAGTTCAACAATAGGAGTGGAGTGTCTGAAGAGAGAGCACAGAGATTTGCGATGATAGCAGGATCTCTCCCTCGGGCATGCAGCAACGGAACCCCGTTCGTCACAGCCGGGGCAGAAGATGATGCACCAGAAGACATCACCGATACCCTGGAGAGGATCCTCTCTATCCAGGCTCAAGTATGGGTCACAGTAGCAAAAGCCATGACTGCGTATGAGACTGCAGATGAGTCGGAAACAAGGCGAATCAATAAGTATATGCAGCAAGGCAGGGTCCAAAAGAAATACATCCTCTACCCCGTATGCAGGAGCACAATCCAACTCACGATCAGACAGTCTCTTGCAGTCCGCATCTTTTTGGTTAGCGAGCTCAAGAGAGGCCGCAACACGGCAGGTGGTACCTCTACTTATTATAACCTGGTAGGGGACGTAGACTCATACATCAGGAATACCGGGCTTACTGCATTCTTCTTGACACTCAAGTACGGAATCAACACCAAGACATCAGCCCTTGCACTTAGTAGCCTCTCAGGCGACATCCAGAAGATGAAGCAGCTCATGCGTTTGTATCGGATGAAAGGAGATAATGCGCCGTACATGACATTACTTGGTGATAGTGACCAGATGAGCTTTGCGCCTGCCGAGTATGCACAACTTTACTCCTTTGCCATGGGTATGGCATCAGTCCTAGATAAAGGTACTGGGAAATACCAATTTGCCAGGGACTTTATGAGCACATCATTCTGGAGACTTGGAGTAGAGTACGCTCAGGCTCAGGGAAGTAGCATTAACGAGGATATGGCTGCCGAGCTAAAGCTAACCCCAGCAGCAATGAAGGGCCTGGCAGCTGCTGCCCAACGGGTCTCCGACGATACCAGCAGCATATACATGCCTACTCAACAAGTCGGAGTCCTCACTGGGCTTAGCGAGGGGGGGTCCCAAGCTCTACAAGGCGGATCGAATAGATCGCAAGGGCAACCAGAAGCCGGGGATGGGGAGACCCAATTCCTGGATCTGATGAGAGCGGTAGCAAATAGCATGAGGGAGGCGCCAAACTCTGCACAGGGCACTCCCCAATCGGGGCCTCCCCCAACTCCTGGGCCATCCCAAGATAACGACACCGACTGGGGGTATTGATGGACAAAACCCAGCCTGCTTCCACAAAAACATCCCAATGCCCTCACCCGTAGTCGACCCCTCGATTTGCGGCTCTATATGACCACACCCTCAAACAAACATCCCCCTCTTTCCTCCCTCCCCCTGCTGTACAACTCCGCACGCCCTAGATACCACAGGCACAATGCGGCTCACTAACAATCAAAACAGAGCCGAGGGAATTAGAAAAAAGTACGGGTAGAAGAGGGATATTCAGAGATCAGGGCAAGTCTCCCGAGTCTCTGCTCTCTCCTCTACCTGATAGACCAGGACAAACATGGCCACCTTTACAGATGCAGAGATCGACGAGCTATTTGAGACAAGTGGAACTGTCATTGACAACATAATTACAGCCCAGGGTAAACCAGCAGAGACTGTTGGAAGGAGTGCAATCCCACAAGGCAAGACCAAGGTGCTGAGCGCAGCATGGGAGAAGCATGGGAGCATCCAGCCACCGGCCAGTCAAGACAACCCCGATCGACAGGACAGATCTGACAAACAACCATCCACACCCGAGCAAACGACCCCGCATGACAGCCCGCCGGCCACATCCGCCGACCAGCCCCCCACCCAGGCCACAGACGAAGCCGTCGACACACAGTTCAGGACCGGAGCAAGCAACTCTCTGCTGTTGATGCTTGACAAGCTCAGCAATAAATCGTCCAATGCTAAAAAGGGCCCATGGTCGAGCCCCCAAGAGGGGAATCACCAACGTCCGACTCAACAGCAGGGGAGTCAACCCAGTCGCGGAAACAGTCAGGAAAGACCGCAGAACCAAGTCAAGGCCGCCCCTGGAAACCAGGGCACAGACGTGAACACAGCATATCATGGACAATGGGAGGAGTCACAACTATCAGCTGGTGCAACCCCTCATGCTCTCCGATCAAGGCAGAGCCAAGACAATACCCTTGTATCTGCGGATCATGTCCAGCCACCTGTAGACTTTGTGCAAGCGATGATGTCTATGATGGAGGCGATATCACAGAGAGTAAGTAAGGTTGACTATCAGCTAGATCTTGTCTTGAAACAGACATCCTCCATCCCTATGATGCGGTCCGAAATCCAACAGCTGAAAACATCTGTTGCAGTCATGGAAGCCAACTTGGGAATGATGAAGATTCTGGATCCCGGTTGTGCCAACATTTCATCTCTGAGTGATCTACGGGCAGTTGCCCGATCTCACCCGGTTTTAGTTTCAGGCCCTGGAGACCCCTCTCCCTATGTGACACAAGGAGGCGAAATGGCACTTAATAAACTTTCGCAACCAGTGCCACATCCATCTGAATTGATTAAACCCGCCACTGCATGCGGGCCTGATATAGGAGTGGAAAAGGACACTGTCCGTGCATTGATCATGTCACGCCCAATGCACCCGAGTTCTTCAGCCAAGCTCCTAAGCAAGTTAGATGCAGCCGGGTCGATCGAGGAAATCAGGAAAATCAAGCGCCTTGCTCTAAATGGCTAATTACTACTGCCACACGTAGCGGGTCCCTGTCCACTCGGCATCACACGGAATCTGCACCGAGTTCCCCCtctagaaaacgcgtACCCAAGGTCCAACTCTCCAAGCGGCAATCCTCTCTCGCTTCCTCAGCCCCACTGAATGGTCGCGTAACCGTAATTAATCTAGCTACATTTAAGATTAAGAAAAAATACGGGTAGAATTGGAGTGCCCCAATTGTGCCAAGATGGACTCATCTAGGACAATTGGGCTGTACTTTGATTCTGCCCATTCTTCTAGCAACCTGTTAGCATTTCCGATCGTCCTACAAGGCACAGGAGATGGGAAGAAGCAAATCGCCCCGCAATATAGGATCCAGCGCCTTGACTTGTGGACTGATAGTAAGGAGGACTCAGTATTCATCACCACCTATGGATTCATCTTTCAAGTTGGGAATGAAGAAGCCACTGTCGGCATGATCGATGATAAACCCAAGCGCGAGTTACTTTCCGCTGCGATGCTCTGCCTAGGAAGCGTCCCAAATACCGGAGACCTTATTGAGCTGGCAAGGGCCTGTCTCACTATGATAGTCACATGCAAGAAGAGTGCAACTAATACTGAGAGAATGGTTTTCTCAGTAGTGCAGGCACCCCAAGTGCTGCAAAGCTGTAGGGTTGTGGCAAACAAATACTCATCAGTGAATGCAGTCAAGCACGTGAAAGCGCCAGAGAAGATTCCCGGGAGTGGAACCCTAGAATACAAGGTGAACTTTGTCTCCTTGACTGTGGTACCGAAGAAGGATGTCTACAAGATCCCAGCTGCAGTATTGAAGGTTTCTGGCTCGAGTCTGTACAATCTTGCGCTCAATGTCACTATTAATGTGGAGGTAGACCCGAGGAGTCCTTTGGTTAAATCTTTGTCTAAGTCTGACAGCGGATACTATGCTAACCTCTTCTTGCATATTGGACTTATGACCACCGTAGATAGGAAGGGGAAGAAAGTGACATTTGACAAGCTGGAAAAGAAAATAAGGAGCCTTGATCTATCTGTCGGGCTCAGTGATGTGCTCGGGCCTTCCGTGTTGGTAAAAGCAAGAGGTGCACGGACTAAGCTTTTGGCACCTTTCTTCTCTAGCAGTGGGACAGCCTGCTATCCCATAGCAAATGCTTCTCCTCAGGTGGCCAAGATACTCTGGAGTCAAACCGCGTGCCTGCGGAGCGTTAAAATCATTATCCAAGCAGGTACCCAACGCGCTGTCGCAGTGACCGCCGACCACGAGGTTACCTCTACTAAGCTGGAGAAGGGGCACACCCTTGCCAAATACAATCCTTTTAAGAAATAAGCTGCGTCTCTGAGATTGCGCTCCGCCCACTCACCCAGATCATCATGACACAAAAAACTAATCTGTCTTGATTATTTACAGTTAGTTTACCTGTCTATCAAGTTAGAAAAAACACGGGTAGAAGATTCTGGATCCCGGTTGGCGCCCTCCAGGTGCAAGttaattaaATGGGCTCCAGACCTTCTACCAAGAACCCAGCACCTATGATGCTGACTATCCGGGTTGCGCTGGTACTGAGTTGCATCTGTCCGGCAAACTCCATTGATGGCAGGCCTCTTGCAGCTGCAGGAATTGTGGTTACAGGAGACAAAGCCGTCAACATATACACCTCATCCCAGACAGGATCAATCATAGTTAAGCTCCTCCCGAATCTGCCCAAGGATAAGGAGGCATGTGCGAAAGCCCCCTTGGATGCATACAACAGGACATTGACCACTTTGCTCACCCCCCTTGGTGACTCTATCCGTAGGATACAAGAGTCTGTGACTACATCTGGAGGGGGGAGACAGGGGCGCCTTATAGGCGCCATTATTGGCGGTGTGGCTCTTGGGGTTGCAACTGCCGCACAAATAACAGCGGCCGCAGCTCTGATACAAGCCAAACAAAATGCTGCCAACATCCTCCGACTTAAAGAGAGCATTGCCGCAACCAATGAGGCTGTGCATGAGGTCACTGACGGATTATCGCAACTAGCAGTGGCAGTTGGGAAGATGCAGCAGTTTGTTAATGACCAATTTAATAAAACAGCTCAGGAATTAGACTGCATCAAAATTGCACAGCAAGTTGGTGTAGAGCTCAACCTGTACCTAACCGAATTGACTACAGTATTCGGACCACAAATCACTTCACCTGCTTTAAACAAGCTGACTATTCAGGCACTTTACAATCTAGCTGGTGGAAATATGGATTACTTATTGACTAAGTTAGGTGTAGGGAACAATCAACTCAGCTCATTAATCGGTAGCGGCTTAATCACtGGcAACCCTATTCTATACGACTCACAGACTCAACTCTTGGGTATACAGGTAACTgcaCCTTCAGTCGGGAACCTAAATAATATGCGTGCCACCTACTTGGAAACCTTATCCGTAAGCACAACCAGGGGATTTGCCTCGGCACTTGTCCCCAAAGTGGTGACACAGGTCGGTTCTGTGATAGAAGAACTTGACACCTCATACTGTATAGAAACTGACTTAGATTTATATTGTACAAGAATAGTAACGTTCCCTATGTCCCCTGGTATTTATTCCTGCTTGAGCGGCAATACGTCGGCCTGTATGTACTCAAAGACCGAAGGCGCACTTACTACACCATACATGACTATCAAAGGTTCAGTCATCGCCAACTGCAAGATGACAACATGTAGATGTGTAAACCCCCCGGGTATCATATCGCAAAACTATGGAGAAGCCGTGTCTCTAATAGATAAACAATCATGCAATGTTTTATCCTTAGGCGGGATAACTTTAAGGCTCAGTGGGGAATTCGATGTAACTTATCAGAAGAATATCTCAATACAAGATTCTCAAGTAATAATAACAGGCAATCTTGATATCTCAACTGAGCTTGGGAATGTCAACAACTCGATCAGTAATGCTTTGAATAAGTTAGAGGAAAGCAACAGAAAACTAGACAAAGTCAATGTCAAACTGACTAGCACATCTGCTCTCATTACgTATATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTGATTCTAGCATGCTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTTATTATGGCTTGGGAATAATACaCTcGATCAGATGAGAGCCACTACAAAAATGTGAACACAGATGAGGAACGAAGGTTTCCCTAATAGTAATTTGTGTGAAAGTTCTGGTAGTCTGTCAGTTCAGAGAGTTAAGAAAAAACTACCGGTTGTAGATGACCAAAGGACGATATACGGGTAGAACGGTAAGAGAGGCCGCCCCTCAATTGCGAGCCAGGCTTCACAACCTCCGTTCTACCGCTTCACCGACAACAGTCCTCAATCATGGACCGCGCCGTTAGCCAAGTTGCGTTAGAGAATGATGAAAGAGAGGCAAAAAATACATGGCGCTTGATATTCCGGATTGCAATCTTATTCTTAACAGTAGTGACCTTGGCTATATCTGTAGCCTCCCTTTTATATAGCATGGGGGCTAGCACACCTAGCGATCTTGTAGGCATACCGACTAGGATTTCCAGGGCAGAAGAAAAGATTACATCTACACTTGGTTCCAATCAAGATGTAGTAGATAGGATATATAAGCAAGTGGCCCTTGAGTCTCCGTTGGCATTGTTAAATACTGAGACCACAATTATGAACGCAATAACATCTCTCTCTTATCAGATTAATGGAGCTGCAAACAACAGTGGGTGGGGGGCACCTATCCATGACCCAGATTATATAGGGGGGATAGGCAAAGAACTCATTGTAGATGATGCTAGTGATGTCACATCATTCTATCCCTCTGCATTTCAAGAACATCTGAATTTTATCCCGGCGCCTACTACAGGATCAGGTTGCACTCGAATACCCTCATTTGACATGAGTGCTACCCATTACTGCTACACCCATAATGTAATATTGTCTGGATGCAGAGATCACTCACATTCATATCAGTATTTAGCACTTGGTGTGCTCCGGACATCTGCAACAGGGAGGGTATTCTTTTCTACTCTGCGTTCCATCAACCTGGACGACACCCAAAATCGGAAGTCTTGCAGTGTGAGTGCAACTCCCCTGGGTTGTGATATGCTGTGCTCGAAAGTCACGGAGACAGAGGAAGAAGATTATAACTCAGCTGTCCCTACGCGGATGGTACATGGGAGGTTAGGGTTCGACGGCCAGTACCACGAAAAGGACCTAGATGTCACAACATTATTCGGGGACTGGGTGGCCAACTACCCAGGAGTAGGGGGTGGATCTTTTATTGACAGCCGCGTATGGTTCTCAGTCTACGGAGGGTTAAAACCCAATTCACCCAGTGACACTGTACAGGAAGGGAAATATGTGATATACAAGCGATACAATGACACATGCCCAGATGAGCAAGACTACCAGATTCGAATGGCCAAGTCTTCGTATAAGCCTGGACGGTTTGGTGGGAAACGCATACAGCAGGCTATCTTATCTATCAAGGTGTCAACATCCTTAGGCGAAGACCCGGTACTGACTGTACCGCCCAACACAGTCACACTCATGGGGGCCGAAGGCAGAATTCTCACAGTAGGGACATCTCATTTCTTGTATCAACGAGGGTCATCATACTTCTCTCCCGCGTTATTATATCCTATGACAGTCAGCAACAAAACAGCCACTCTTCATAGTCCTTATACATTCAATGCCTTCACTCGGCCAGGTAGTATCCCTTGCCAGGCTTCAGCAAGATGCCCCAACTCGTGTGTTACTGGAGTCTATACAGATCCATATCCCCTAATCTTCTATAGAAACCACACCTTGCGAGGGGTATTCGGGACAATGCTTGATGGTGTACAAGCAAGACTTAACCCTGCGTCTGCAGTATTCGATAGCACATCCCGCAGTCGCATTACTCGAGTGAGTTCAAGCAGTACCAAAGCAGCATACACAACATCAACTTGTTTTAAAGTGGTCAAGACTAATAAGACCTATTGTCTCAGCATTGCTGAAATATCTAATACTCTCTTCGGAGAATTCAGAATCGTCCCGTTACTAGTTGAGATCCTCAAAGATGACGGGGTTAGAGAAGCCAGGTCTGGCTAGggcgcgccTTGAGTCAATTATAAAGGAGTTGGAAAGATGGCATTGTATCACCTATCTTCTGCGACATCAAGAATCAAACCGAATGCCGGCGCGTGCTCGAATTCCATGTTGCCAGTTGACCACAATCAGCCAGTGCTCATGCGATCAGATTAAGCCTTGTCATTAATCTCTTGATTAAGAAAAAATGTAAGTGGCAATGAGATACAAGGCAAAACAGCTCATGGTAAATAATACGGGTAGGACATGGCGAGCTCCGGTCCTGAAAGGGCAGAGCATCAGATTATCCTACCAGAGCCACACCTGTCTTCACCATTGGTCAAGCACAAACTACTCTATTACTGGAAATTAACTGGGCTACCGCTTCCTGATGAATGTGACTTCGACCACCTCATTCTCAGCCGACAATGGAAAAAAATACTTGAATCGGCCTCTCCTGATACTGAGAGAATGATAAAACTCGGAAGGGCAGTACACCAAACTCTTAACCACAATTCCAGAATAACCGGAGTGCTCCACCCCAGGTGTTTAGAACAACTGGCTAATATTGAGGTCCCAGATTCAACCAACAAATTTCGGAAGATTGAGAAGAAGATCCAAATTCACAACACGAGATATGGAGAACTGTTCACAAGGCTGTGTACGCATATAGAGAAGAAACTGCTGGGGTCATCTTGGTCTAACAATGTCCCCCGGTCAGAGGAGTTCAGCAGCATTCGTACGGATCCGGCATTCTGGTTTCACTCAAAATGGTCCACAGCCAAGTTTGCATGGCTCCATATAAAACAGATCCAGAGGCATCTGATGGTGGCAGCTAAGACAAGGTCTGCGGCCAACAAATTGGTGATGCTAACCCATAAGGTAGGCCAAGTCTTTGTCACTCCTGAACTTGTCGTTGTGACGCATACGAATGAGAACAAGTTCACATGTCTTACCCAGGAACTTGTATTGATGTATGCAGATATGATGGAGGGCAGAGATATGGTCAACATAATATCAACCACGGCGGTGCATCTCAGAAGCTTATCAGAGAAAATTGATGACATTTTGCGGTTAATAGACGCTCTGGCAAAAGACTTGGGTAATCAAGTCTACGATGTTGTATCACTAATGGAGGGATTTGCATACGGAGCTGTCCAGCTACTCGAGCCGTCAGGTACATTTGCAGGAGATTTCTTCGCATTCAACCTGCAGGAGCTTAAAGACATTCTAATTGGCCTCCTCCCCAATGATATAGCAGAATCCGTGACTCATGCAATCGCTACTGTATTCTCTGGTTTAGAACAGAATCAAGCAGCTGAGATGTTGTGTCTGTTGCGTCTGTGGGGTCACCCACTGCTTGAGTCCCGTATTGCAGCAAAGGCAGTCAGGAGCCAAATGTGCGCACCGAAAATGGTAGACTTTGATATGATCCTTCAGGTACTGTCTTTCTTCAAGGGAACAATCATCAACGGGTACAGAAAGAAGAATGCAGGTGTGTGGCCGCGAGTCAAAGTGGATACAATATATGGGAAGGTCATTGGGCAACTACATGCAGATTCAGCAGAGATTTCACACGATATCATGTTGAGAGAGTATAAGAGTTTATCTGCACTTGAATTTGAGCCATGTATAGAATATGACCCTGTCACCAACCTGAGCATGTTCCTAAAAGACAAGGCAATCGCACACCCCAACGATAATTGGCTTGCCTCGTTTAGGCGGAACCTTCTCTCCGAAGACCAGAAGAAACATGTAAAAGAAGCAACTTCGACTAATCGCCTCTTGATAGAGTTTTTAGAGTCAAATGATTTTGATCCATATAAAGAGATGGAATATCTGACGACCCTTGAGTACCTTAGAGATGACAATGTGGCAGTATCATACTCGCTCAAGGAGAAGGAAGTGAAAGTTAATGGACGGATCTTCGCTAAGCTGACAAAGAAGTTAAGGAACTGTCAGGTGATGGCGGAAGGGATCCTAGCCGATCAGATTGCACCTTTCTTTCAGGGAAATGGAGTCATTCAGGATAGCATATCCTTGACCAAGAGTATGCTAGCGATGAGTCAACTGTCTTTTAACAGCAATAAGAAACGTATCACTGACTGTAAAGAAAGAGTATCTTCAAACCGCAATCATGATCCGAAAAGCAAGAACCGTCGGAGAGTTGCAACCTTCATAACAACTGACCTGCAAAAGTACTGTCTTAATTGGAGATATCAGACAATCAAATTGTTCGCTCATGCCATCAATCAGTTGATGGGCCTACCTCACTTCTTCGAATGGATTCACCTAAGACTGATGGACACTACGATGTTCGTAGGAGACCCTTTCAATCCTCCAAGTGACCCTACTGACTGTGACCTCTCAAGAGTCCCTAATGATGACATATATATTGTCAGTGCCAGAGGGGGTATCGAAGGATTATGCCAGAAGCTATGGACAATGATCTCAATTGCTGCAATCCAACTTGCTGCAGCTAGATCGCATTGTCGTGTTGCCTGTATGGTACAGGGTGATAATCAAGTAATAGCAGTAACGAGAGAGGTAAGATCAGACGACTCTCCGGAGATGGTGTTGACACAGTTGCATCAAGCCAGTGATAATTTCTTCAAGGAATTAATTCATGTCAATCATTTGATTGGCCATAATTTGAAGGATCGTGAAACCATCAGGTCAGACACATTCTTCATATACAGCAAACGAATCTTCAAAGATGGAGCAATCCTCAGTCAAGTCCTCAAAAATTCATCTAAATTAGTGCTAGTGTCAGGTGATCTCAGTGAAAACACCGTAATGTCCTGTGCCAACATTGCCTCTACTGTAGCACGGCTATGCGAGAACGGGCTTCCCAAAGACTTCTGTTACTATTTAAACTATATAATGAGTTGTGTGCAGACATACTTTGACTCTGAGTTCTCCATCACCAACAATTCGCACCCCGATCTTAATCAGTCGTGGATTGAGGACATCTCTTTTGTGCACTCATATGTTCTGACTCCTGCCCAATTAGGGGGACTGAGTAACCTTCAATACTCAAGGCTCTACACTAGAAATATCGGTGACCCGGGGACTACTGCTTTTGCAGAGATCAAGCGACTAGAAGCAGTGGGATTACTGAGTCCTAACATTATGACTAATATCTTAACTAGGCCGCCTGGGAATGGAGATTGGGCCAGTCTGTGCAACGACCCATACTCTTTCAATTTTGAGACTGTTGCAAGCCCAAATATTGTTCTTAAGAAACATACGCAAAGAGTCCTATTTGAAACTTGTTCAAATCCCTTATTGTCTGGAGTGCACACAGAGGATAATGAGGCAGAAGAGAAGGCATTGGCTGAATTCTTGCTTAATCAAGAGGTGATTCATCCCCGCGTTGCGCATGCCATCATGGAGGCAAGCTCTGTAGGTAGGAGAAAGCAAATTCAAGGGCTTGTTGACACAACAAACACCGTAATTAAGATTGCGCTTACTAGGAGGCCATTAGGCATCAAGAGGCTGATGCGGATAGTCAATTATTCTAGCATGCATGCAATGCTGTTTAGAGACGATGTTTTTTCCTCCAGTAGATCCAACCACCCCTTAGTCTCTTCTAATATGTGTTCTCTGACACTGGCAGACTATGCACGGAATAGAAGCTGGTCACCTTTGACGGGAGGCAGGAAAATACTGGGTGTATCTAATCCTGATACGATAGAACTCGTAGAGGGTGAGATTCTTAGTGTAAGCGGAGGGTGTACAAGATGTGACAGCGGAGATGAACAATTTACTTGGTTCCATCTTCCAAGCAATATAGAATTGACCGATGACACCAGCAAGAATCCTCCGATGAGGGTACCATATCTCGGGTCAAAGACACAGGAGAGGAGAGCTGCCTCACTTGCAAAAATAGCTCATATGTCGCCACATGTAAAGGCTGCCCTAAGGGCATCATCCGTGTTGATCTGGGCTTATGGGGATAATGAAGTAAATTGGACTGCTGCTCTTACGATTGCAAAATCTCGGTGTAATGTAAACTTAGAGTATCTTCGGTTACTGTCCCCTTTACCCACGGCTGGGAATCTTCAACATAGACTAGATGATGGTATAACTCAGATGACATTCACCCCTGCATCTCTCTACAGGgtgtcaccttacattcacatatccaatgattctcaaaggctgttcactgaagaaggagtcaaagaggggaatgtggtttaccaacagatcATGCTCTTGGGTTTATCTCTAATCGAATCGATCTTTCCAATGACAACAACCAGGACATATGATGAGATCACACTGCACCTACATAGTAAATTTAGTTGCTGTATCAGAGAAGCACCTGTTGCGGTTCCTTTCGAGCTACTTGGGGTGGTACCGGAACTGAGGACAGTGACCTCAAATAAGTTTATGTATGATCCTAGCCCTGTATCGGAGGGAGACTTTGCGAGACTTGACTTAGCTATCTTCAAGAGTTATGAGCTTAATCTGGAGTCATATCCCACGATAGAGCTAATGAACATTCTTTCAATATCCAGCGGGAAGTTGATTGGCCAGTCTGTGGTTTCTTATGATGAAGATACCTCCATAAAGAATGACGCCATAATAGTGTATGACAATACCCGAAATTGGATCAGTGAAGCTCAGAATTCAGATGTGGTCCGCCTATTTGAATATGCAGCACTTGAAGTGCTCCTCGACTGTTCTTACCAACTCTATTACCTGAGAGTAAGAGGCCTAGACAATATTGTCTTATATATGGGTGATTTATACAAGAATATGCCAGGAATTCTACTTTCCAACATTGCAGCTACAATATCTCATCCCGTCATTCATTCAAGGTTACATGCAGTGGGCCTGGTCAACCATGACGGATCACACCAACTTGCAGATACGGATTTTATCGAAATGTCTGCAAAACTATTAGTATCTTGCACCCGACGTGTGATCTCCGGCTTATATTCAGGAAATAAGTATGATCTGCTGTTCCCATCTGTCTTAGATGATAACCTGAATGAGAAGATGCTTCAGCTGATATCCCGGTTATGCTGTCTGTACACGGTACTCTTTGCTACAACAAGAGAAATCCCGAAAATAAGAGGCTTAACTGCAGAAGAGAAATGTTCAATACTCACTGAGTATTTACTGTCGGATGCTGTGAAACCATTACTTAGCCCCGATCAAGTGAGCTCTATCATGTCTCCTAACATAATTACATTCCCAGCTAATCTGTACTACATGTCTCGGAAGAGCCTCAATTTGATCAGGGAAAGGGAGGACAGGGATACTATCCTGGCGTTGTTGTTCCCCCAAGAGCCATTATTAGAGTTCCCTTCTGTGCAAGATATTGGTGCTCGAGTGAAAGATCCATTCACCCGACAACCTGCGGCATTTTTGCAAGAGTTAGATTTGAGTGCTCCAGCAAGGTATGACGCATTCACACTTAGTCAGATTCATCCTGAACTCACATCTCCAAATCCGGAGGAAGACTACTTAGTACGATACTTGTTCAGAGGGATAGGGACTGCATCTTCCTCTTGGTATAAGGCATCTCATCTCCTTTCTGTACCCGAGGTAAGATGTGCAAGACACGGGAACTCCTTATACTTAGCTGAAGGGAGCGGAGCCATCATGAGTCTTCTCGAACTGCATGTACCACATGAAACTATCTATTACAATACGCTCTTTTCAAATGAGATGAACCCCCCGCAACGACATTTCGGGCCGACCCCAACTCAGTTTTTGAATTCGGTTGTTTATAGGAATCTACAGGCGGAGGTAACATGCAAAGATGGATTTGTCCAAGAGTTCCGTCCATTATGGAGAGAAAATACAGAGGAAAGTGACCTGACCTCAGATAAAGCAGTGGGGTATATTACATCTGCAGTGCCCTACAGATCTGTATCATTGCTGCATTGTGACATTGAAATTCCTCCAGGGTCCAATCAAAGCTTACTAGATCAACTAGCTATCAATTTATCTCTGATTGCCATGCATTCTGTAAGGGAGGGCGGGGTAGTAATCATCAAAGTGTTGTATGCAATGGGATACTACTTTCATCTACTCATGAACTTGTTTGCTCCGTGTTCCACAAAAGGATATATTCTCTCTAATGGTTATGCATGTCGAGGAGATATGGAGTGTTACCTGGTATTTGTCATGGGTTACCTGGGCGGGCCTACATTTGTACATGAGGTGGTGAGGATGGCAAAAACTCTGGTGCAGCGGCACGGTACGCTCTTGTCTAAATCAGATGAGATCACACTGACCAGGTTATTCACCTCACAGCGGCAGCGTGTGACAGACATCCTATCCAGTCCTTTACCAAGATTAATAAAGTACTTGAGGAAGAATATTGACACTGCGCTGATTGAAGCCGGGGGACAGCCCGTCCGTCCATTCTGTGCGGAGAGTCTGGTGAGCACGCTAGCGAACATAACTCAGATAACCCAGATTATCGCTAGTCACATTGACACAGTTATCCGGTCTGTGATATATATGGAAGCTGAGGGTGATCTCGCTGACACAGTATTTCTATTTACCCCTTACAATCTCTCTACTGACGGGAAAAAGAGGACATCACTTATACAGTGCACGAGACAGATCCTAGAGGTTACAATACTAGGTCTTAGAGTCGAAAATCTCAATAAAATAGGCGATATAATCAGCCTAGTGCTTAAAGGCATGATCTCCATGGAGGACCTTATCCCACTAAGGACATACTTGAAGCATAGTACCTGCCCTAAATATTTGAAGGCTGTCCTAGGTATTACCAAACTCAAAGAAATGTTTACAGACACTTCTGTATTGTACTTGACTCGTGCTCAACAAAAATTCTACATGAAAACTATAGGCAATGCAGTCAAAGGATATTACAGTAACTGTGACTCTTAACGAAAATCACATATTAATAGGCTCCTTTTTTGGCCAATTGTATTCTTGTTGATTTAATCATATTATGTTAGAAAAAAGTTGAACCCTGACTCCTTAGGACTCGAATTCGAACTCAAATAAATGTCTTAAAAAAAGGTTGCGCACAATTATTCTTGAGTGTAGTCTCGTCATTCACCAAATCTTTGTTTGGTGGCCGGCATGGTCCCAGCCTCCTCGCTGGCGCCGGCTGGGCAACATTCCGAGGGGACCGTCCCCTCGGTAATGGCGAATGGGACGTCGACTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTATAT SEQ ID NO:MASSGPERAEHQIILPEPHLSSPLVKHKLLYYWKLTGLPLPDECDFDHLILSRQWKKILE11; StabilizedSASPDTERMIKLGRAVHQTLNHNSRITGVLHPRCLEQLANIEVPDSTNKFRKIEKKIQIH L proteinNTRYGELFTRLCTHIEKKLLGSSWSNNVPRSEEFSSIRTDPAFWFHSKWSTAKFAWLHIK sequenceQIQRHLMVAAKTRSAANKLVMLTHKVGQVFVTPELVVVTHTNENKFTCLTQELVLMYADM (2204 aa)MEGRDMVNIISTTAVHLRSLSEKIDDILRLIDALAKDLGNQVYDVVSLMEGFAYGAVQLLEPSGTFAGDFFAFNLQELKDILIGLLPNDIAESVTHAIATVFSGLEQNQAAEMLCLLRLWGHPLLESRIAAKAVRSQMCAPKMVDFDMILQVLSFFKGTIINGYRKKNAGVWPRVKVDTIYGKVIGQLHADSAEISHDIMLREYKSLSALEFEPCIEYDPVTNLSMFLKDKAIAHPNDNWLASFRRNLLSEDQKKHVKEATSTNRLLIEFLESNDFDPYKEMEYLTTLEYLRDDNVAVSYSLKEKEVKVNGRIFAKLTKKLRNCQVMAEGILADQIAPFFQGNGVIQDSISLTKSMLAMSQLSFNSNKKRITDCKERVSSNRNHDPKSKNRRRVATFITTDLQKYCLNWRYQTIKLFAHAINQLMGLPHFFEWIHLRLMDTTMFVGDPFNPPSDPTDCDLSRVPNDDIYIVSARGGIEGLCQKLWTMISIAAIQLAAARSHCRVACMVQGDNQVIAVTREVRSDDSPEMVLTQLHQASDNFFKELIHVNHLIGHNLKDRETIRSDTFFIYSKRIFKDGAILSQVLKNSSKLVLVSGDLSENTVMSCANIASTVARLCENGLPKDFCYYLNYIMSCVQTYFDSEFSITNNSHPDLNQSWIEDISFVHSYVLTPAQLGGLSNLQYSRLYTRNIGDPGTTAFAEIKRLEAVGLLSPNIMTNILTRPPGNGDWASLCNDPYSFNFETVASPNIVLKKHTQRVLFETCSNPLLSGVHTEDNEAEEKALAEFLLNQEVIHPRVAHAIMEASSVGRRKQIQGLVDTTNTVIKIALTRRPLGIKRLMRIVNYSSMHAMLFRDDVFSSSRSNHPLVSSNMCSLTLADYARNRSWSPLTGGRKILGVSNPDTIELVEGEILSVSGGCTRCDSGDEQFTWFHLPSNIELTDDTSKNPPMRVPYLGSKTQERRAASLAKIAHMSPHVKAALRASSVLIWAYGDNEVNWTAALTIAKSRCNVNLEYLRLLSPLPTAGNLQHRLDDGITQMTFTPASLYRVSPYIHISNDSQRLFTEEGVKEGNVVYQQIMLLGLSLIESIFPMTTTRTYDEITLHLHSKFSCCIREAPVAVPFELLGVVPELRTVTSNKFMYDPSPVSEGDFARLDLAIFKSYELNLESYPTIELMNILSISSGKLIGQSVVSYDEDTSIKNDAIIVYDNTRNWISEAQNSDVVRLFEYAALEVLLDCSYQLYYLRVRGLDNIVLYMGDLYKNMPGILLSNIAATISHPVIHSRLHAVGLVNHDGSHQLADTDFIEMSAKLLVSCTRRVISGLYSGNKYDLLFPSVLDDNLNEKMLQLISRLCCLYTVLFATTREIPKIRGLTAEEKCSILTEYLLSDAVKPLLSPDQVSSIMSPNIITFPANLYYMSRKSLNLIREREDRDTILALLFPQEPLLEFPSVQDIGARVKDPFTRQPAAFLQELDLSAPARYDAFTLSQIHPELTSPNPEEDYLVRYLFRGIGTASSSWYKASHLLSVPEVRCARHGNSLYLAEGSGAIMSLLELHVPHETIYYNTLFSNEMNPPQRHFGPTPTQFLNSVVYRNLQAEVTCKDGFVQEFRPLWRENTEESDLTSDKAVGYITSAVPYRSVSLLHCDIEIPPGSNQSLLDQLAINLSLIAMHSVREGGVVIIKVLYAMGYYFHLLMNLFAPCSTKGYILSNGYACRGDMECYLVFVMGYLGGPTFVHEVVRMAKTLVQRHGTLLSKSDEITLTRLFTSQRQRVTDILSSPLPRLIKYLRKNIDTALIEAGGQPVRPFCAESLVSTLANITQITQIIASHIDTVIRSVIYMEAEGDLADTVFLFTPYNLSTDGKKRTSLIQCTRQILEVTILGLRVENLNKIGDIISLVLKGMISMEDLIPLRTYLKHSTCPKYLKAVLGITKLKEMFTDTSVLYLTRAQQKFYMKTIGNAVKGYYSNCDS SEQ ID NO:MLQLPLTILLSILSAHQSLCLDNSKLIHAGIMSTTEREVNVYAQSITGSIVVRLIPNIPS12; ChimericNHKSCATSQIKLYNDTLTRLLTPIKANLEGLISAVSQDQSQNSGKRKKRFVGAVIGAAAL APMV-5-GLATAAQVTATVALNQAQENARNILRLKNSIQKTNEAVMELKDAVGQTAVAIDKTQAFIN NDV F geneNQILPAISNLSCEVLGNKIGVQLSLYLTELTTVFGNQLTNPALTTLSLQALYNLCGDDFN (546 aa)YLINLLNAKNRNLASLYEANLIQGRITQYDSMNQLLIIQVQIPSISTVSGMRVTELFTLSVDTPIGEGKALVPKYVLSSGRIMEEVDLSSCAITSTSVFCSSIISRPLPLETINCLNGNVTQCQFTANTGTLESRYAVIGGLVIANCKAIVCRCLNPPGVIAQNLGLPITIISSNTCQRINLEQITLSLGNSILSTYSANLSQVEMNLAPSNPLDISVELNRVNTSLSKVESLIKESNSILDSVNPQILNVKTLITYIVLTIISLVFGILSLILACYLMYKQKAQQKTLLWLGNNTLDQM RATTKMSEQ ID NO: MDRAVSQVALENDEREAKNTWRLIFRIAILFLTVVTLAISVASLLYSMGASTPSTLISLN13; ChimericNSIITSSNGLKKEILNQNIKEDLIYREVAINIPLTLDRVTVEVGTAVNQITDALRQLQSV NDV-APMV-NGSAAFASSNSPDYSGGIEHLIFQRNTLINRSVSVSDLIEHPSFIPTPTTQHGCTRIPTF 5 HN geneHLGTRHWCYSHNIIGQGCADSRASVMYISMGALGVSSLGTPTFTTSAASILSDSLNRKSC (576 aa)SIVATTEGCDVLCSIVTQTEDQDYADHTPTPMIHGRLWFNGTYTERSLSQSLFLGTWAAQ UnderlinedYPAVGSGIMTPGRVIFPFYGGVIPNSPLFLDLERFALFTHNGDLECMNLTQYQKEAIYSA part fromYKPPKIRGSLWAQGFIVCSVGDMGNCSLKVINTSTVMMGAEGRLQLVGDSVMYYQRSSSW NDV;WPVGILYRLSLVDIIAGDIQVVINSEPLPLSKFPRPTWTPGVCQKPNVCPAVCVTGVYQD remainingLWAISAGETLSEMTFFGGYLEASTQRKDPWIGVANQYSWFMRRRLFKTSTEAAYSSSTCF part fromRNTRLDRNFCLLVFELTDNLLGDWRIVPLLFELTIV APMV5 SEQ ID NO:MLQLPLTILLSILSAHQSLCLDNSKLIHAGIMSTTEREVNVYAQSITGSIVVRLIPNIPS14; wt APMV-NHKSCATSQIKLYNDTLTRLLTPIKANLEGLISAVSQDQSQNSGKRKKRFVGAVIGAAAL 5 FGLATAAQVTATVALNQAQENARNILRLKNSIQKTNEAVMELKDAVGQTAVAIDKTQAFIN(YP_009094158.1;NQILPAISNLSCEVLGNKIGVQLSLYLTELTTVFGNQLTNPALTTLSLQALYNLCGDDFN 544YLINLLNAKNRNLASLYEANLIQGRITQYDSMNQLLIIQVQIPSISTVSGMRVTELFTLS aa)VDTPIGEGKALVPKYVLSSGRIMEEVDLSSCAITSTSVFCSSIISRPLPLETINCLNGNVTQCQFTANTGTLESRYAVIGGLVIANCKAIVCRCLNPPGVIAQNLGLPITIISSNTCQRINLEQITLSLGNSILSTYSANLSQVEMNLAPSNPLDISVELNRVNTSLSKVESLIKESNSILDSVNPQILNVKTVIILAVIIGLIVVWCFILTCLIVRGFMLLVKQQKFKGLSVQNNPYVS NNSHSEQ ID NO: MDKSYYIEPEDQRGNSRTWRLLFRLIVLTLLCLIACILVSQLFYPWLPQVLSTLISLNNS15; wt APMV-IITSSNGLKKEILNQNIKEDLIYREVAINIPLTLDRVTVEVGTAVNQITDALRQLQSVNG5 HN (574 aa)SAAFASSNSPDYSGGIEHLIFQRNTLINRSVSVSDLIEHPSFIPTPTTQHGCTRIPTFHLGTRHWCYSHNIIGQGCADSRASVMYISMGALGVSSLGTPTFTTSAASILSDSLNRKSCSIVATTEGCDVLCSIVTQTEDQDYADHTPTPMIHGRLWFNGTYTERSLSQSLFLGTWAAQYPAVGSGIMTPGRVIFPFYGGVIPNSPLFLDLERFALFTHNGDLECMNLTQYQKEAIYSAYKPPKIRGSLWAQGFIVCSVGDMGNCSLKVINTSTVMMGAEGRLQLVGDSVMYYQRSSSWWPVGILYRLSLVDIIAGDIQVVINSEPLPLSKFPRPTWTPGVCQKPNVCPAVCVTGVYQDLWAISAGETLSEMTFFGGYLEASTQRKDPWIGVANQYSWFMRRRLFKTSTEAAYSSSTCFRNTRLDRNFCLLVFELTDNLLGDWRIVPLLFELTIV SEQ ID NO:MASSGPERAEHQIILPEPHLSSPLVKHKLLYYWKLTGLPLPDECDFDHLILSRQWKKILE16; wild typeSASPDTERMIKLGRAVHQTLNHNSRITGVLHPRCLEQLANIEVPDSTNKFRKIEKKIQIH L proteinNTRYGELFTRLCTHIEKKLLGSSWSNNVPRSEEFSSIRTDPAFWFHSKWSTAKFAWLHIK amino acidQIQRHLMVAAKTRSAANKLVMLTHKVGQVFVTPELVVVTHTNENKFTCLTQELVLMYADM sequenceMEGRDMVNIISTTAVHLRSLSEKIDDILRLIDALAKDLGNQVYDVVSLMEGFAYGAVQLL(AAC28375.1;EPSGTFAGDFFAFNLQELKDILIGLLPNDIAESVTHAIATVFSGLEQNQAAEMLCLLRLW 2204 aa)GHPLLESRIAAKAVRSQMCAPKMVDFDMILQVLSFFKGTIINGYRKKNAGVWPRVKVDTIYGKVIGQLHADSAEISHDIMLREYKSLSALEFEPCIEYDPVTNLSMFLKDKAIAHPNDNWLASFRRNLLSEDQKKHVKEATSTNRLLIEFLESNDFDPYKEMEYLTTLEYLRDDNVAVSYSLKEKEVKVNGRIFAKLTKKLRNCQVMAEGILADQIAPFFQGNGVIQDSISLTKSMLAMSQLSFNSNKKRITDCKERVSSNRNHDPKSKNRRRVATFITTDLQKYCLNWRYQTIKLFAHAINQLMGLPHFFEWIHLRLMDTTMFVGDPFNPPSDPTDCDLSRVPNDDIYIVSARGGIEGLCQKLWTMISIAAIQLAAARSHCRVACMVQGDNQVIAVTREVRSDDSPEMVLTQLHQASDNFFKELIHVNHLIGHNLKDRETIRSDTFFIYSKRIFKDGAILSQVLKNSSKLVLVSGDLSENTVMSCANIASTVARLCENGLPKDFCYYLNYIMSCVQTYFDSEFSITNNSHPDLNQSWIEDISFVHSYVLTPAQLGGLSNLQYSRLYTRNIGDPGTTAFAEIKRLEAVGLLSPNIMTNILTRPPGNGDWASLCNDPYSFNFETVASPNIVLKKHTQRVLFETCSNPLLSGVHTEDNEAEEKALAEFLLNQEVIHPRVAHAIMEASSVGRRKQIQGLVDTTNTVIKIALTRRPLGIKRLMRIVNYSSMHAMLFRDDVFSSSRSNHPLVSSNMCSLTLADYARNRSWSPLTGGRKILGVSNPDTIELVEGEILSVSGGCTRCDSGDEQFTWFHLPSNIELTDDTSKNPPMRVPYLGSKTQERRAASLAKIAHMSPHVKAALRASSVLIWAYGDNEVNWTAALTIAKSRCNVNLEYLRLLSPLPTAGNLQHRLDDGITQMTFTPASLYRCHLTFTYPMILKGCSLKKESKRGMWFTNRVMLLGLSLIESIFPMTTTRTYDEITLHLHSKFSCCIREAPVAVPFELLGVVPELRTVTSNKFMYDPSPVSEGDFARLDLAIFKSYELNLESYPTIELMNILSISSGKLIGQSVVSYDEDTSIKNDAIIVYDNTRNWISEAQNSDVVRLFEYAALEVLLDCSYQLYYLRVRGLDNIVLYMGDLYKNMPGILLSNIAATISHPVIHSRLHAVGLVNHDGSHQLADTDFIEMSAKLLVSCTRRVISGLYSGNKYDLLFPSVLDDNLNEKMLQLISRLCCLYTVLFATTREIPKIRGLTAEEKCSILTEYLLSDAVKPLLSPDQVSSIMSPNIITFPANLYYMSRKSLNLIREREDRDTILALLFPQEPLLEFPSVQDIGARVKDPFTRQPAAFLQELDLSAPARYDAFTLSQIHPELTSPNPEEDYLVRYLFRGIGTASSSWYKASHLLSVPEVRCARHGNSLYLAEGSGAIMSLLELHVPHETIYYNTLFSNEMNPPQRHFGPTPTQFLNSVVYRNLQAEVTCKDGFVQEFRPLWRENTEESDLTSDKAVGYITSAVPYRSVSLLHCDIEIPPGSNQSLLDQLAINLSLIAMHSVREGGVVIIKVLYAMGYYFHLLMNLFAPCSTKGYILSNGYACRGDMECYLVFVMGYLGGPTFVHEVVRMAKTLVQRHGTLLSKSDEITLTRLFTSQRQRVTDILSSPLPRLIKYLRKNIDTALIEAGGQPVRPFCAESLVSTLANITQITQIIASHIDTVIRSVIYMEAEGDLADTVFLFTPYNLSTDGKKRTSLIQCTRQILEVTILGLRVENLNKIGDIISLVLKGMISMEDLIPLRTYLKHSTCPKYLKAVLGITKLKEMFTDTSVLYLTRAQQKFYMKTIGNAVKGYYSNCDS SEQ ID NO:ATGTTCGTGTTCCTGGTCCTGCTGCCACTGGTAAGCTCCCAATGTGTAAACTTAACCACA 17; COVID19AGAACCCAGCTCCCACCTGCCTACACCAACAGCTTCACCAGAGGCGTTTATTACCCCGAC S geneAAGGTATTCCGGTCTTCTGTTCTGCACTCTACCCAGGACCTGTTTCTGCCCTTTTTCAGC sequenceAACGTGACATGGTTCCACGCCATCCACGTGTCTGGCACAAACGGCACCAAGCGGTTTGATAATCCTGTGCTCCCTTTCAATGACGGCGTGTACTTCGCCTCTACTGAGAAGAGCAACATCATCCGGGGCTGGATCTTTGGCACAACACTGGACTCTAAAACCCAGAGCCTGCTGATCGTGAACAACGCCACCAACGTGGTGATTAAGGTGTGCGAGTTCCAGTTCTGCAATGACCCTTTCCTCGGCGTGTACTACCACAAGAACAACAAAAGTTGGATGGAAAGCGAATTCAGGGTGTACTCAAGCGCCAACAACTGTACCTTCGAGTACGTGAGCCAGCCTTTCCTGATGGACCTAGAAGGTAAGCAGGGCAATTTCAAGAACCTCAGAGAGTTCGTGTTCAAGAATATTGACGGCTACTTCAAAATCTACAGCAAGCACACCCCAATCAACCTGGTGCGGGACCTGCCCCAGGGCTTTAGCGCGCTGGAGCCTCTGGTGGACCTGCCTATCGGCATCAACATCACCCGGTTCCAGACACTGCTGGCTCTGCATAGAAGCTACCTGACACCTGGCGACAGTTCTTCTGGCTGGACAGCCGGCGCCGCCGCCTACTACGTGGGCTACCTGCAGCCTAGAACATTCCTGCTGAAATACAACGAGAACGGCACGATCACAGACGCCGTGGACTGCGCCCTGGATCCCCTGTCTGAGACAAAGTGCACCCTGAAGTCTTTCACCGTGGAGAAGGGCATCTACCAGACCTCCAACTTCAGAGTGCAGCCTACCGAATCCATCGTGCGCTTTCCCAACATCACCAACCTGTGCCCCTTCGGCGAGGTCTTTAATGCCACGAGATTCGCCAGCGTGTATGCCTGGAACAGAAAGAGAATCAGCAACTGCGTGGCCGACTACAGCGTGCTGTACAACAGCGCCTCTTTCAGCACATTTAAGTGCTACGGAGTGTCTCCTACCAAACTCAACGATCTGTGCTTCACGAACGTGTATGCCGACAGCTTCGTGATCCGAGGAGATGAGGTGCGGCAGATCGCTCCAGGACAGACAGGCAAGATCGCCGACTACAACTACAAGCTGCCCGACGACTTTACCGGCTGCGTGATCGCTTGGAACAGCAATAACCTGGACTCAAAGGTTGGAGGAAACTACAACTACCTGTACAGACTGTTCAGAAAGTCCAACCTGAAGCCCTTCGAGAGAGACATCTCTACAGAAATCTACCAGGCCGGCAGCACCCCATGTAACGGCGTGGAAGGCTTCAACTGCTACTTCCCTCTGCAGTCTTATGGCTTCCAGCCCACAAACGGAGTGGGCTATCAGCCTTACCGCGTGGTTGTCCTGAGCTTTGAGCTGCTGCATGCCCCTGCTACGGTGTGTGGACCTAAGAAGTCCACCAACCTGGTGAAGAACAAGTGTGTGAACTTCAACTTCAACGGCCTGACCGGCACCGGGGTGCTGACAGAGTCTAACAAGAAATTCCTGCCATTCCAGCAATTCGGCCGGGACATCGCCGACACCACCGACGCCGTGCGGGATCCTCAGACCCTCGAAATCCTGGACATCACCCCCTGTAGCTTCGGCGGCGTGAGCGTGATCACCCCTGGCACAAACACCAGCAATCAAGTGGCTGTCCTGTACCAGGATGTCAATTGCACAGAAGTGCCTGTGGCCATCCACGCCGATCAGCTGACCCCCACCTGGCGGGTGTACTCGACAGGAAGCAACGTGTTTCAAACAAGAGCCGGCTGCCTGATCGGGGCCGAGCACGTGAACAATTCCTACGAGTGCGACATCCCCATCGGCGCCGGCATCTGTGCCTCTTACCAGACACAGACCAATTCCCCTCGTAGAGCCAGATCCGTGGCCAGCCAGAGCATCATCGCCTACACCATGAGCCTGGGCGCCGAAAACAGCGTTGCATATTCCAACAACAGCATCGCCATCCCTACCAACTTCACCATCAGCGTGACCACAGAAATCCTGCCTGTGTCCATGACCAAGACAAGCGTTGATTGCACCATGTACATCTGCGGCGATAGCACAGAGTGCAGCAATCTGCTGCTGCAGTACGGTAGCTTCTGCACCCAGCTGAATAGAGCCCTGACCGGCATCGCTGTGGAACAGGACAAAAACACCCAGGAGGTCTTCGCCCAGGTGAAGCAAATCTACAAGACCCCTCCAATCAAGGACTTCGGAGGCTTTAACTTTAGCCAGATCCTGCCTGATCCCTCCAAGCCTAGCAAACGGAGTTTCATCGAGGACCTGCTCTTCAACAAGGTGACCCTGGCTGACGCCGGCTTCATTAAGCAGTACGGCGATTGCCTCGGCGACATCGCTGCAAGAGACCTGATCTGCGCCCAGAAGTTCAACGGCCTGACCGTGCTGCCTCCTCTCCTGACAGACGAGATGATCGCCCAGTACACCTCTGCCCTTCTGGCTGGCACCATCACCAGCGGATGGACCTTTGGAGCCGGAGCCGCCCTGCAGATCCCTTTCGCTATGCAGATGGCCTACAGATTCAACGGGATCGGAGTGACCCAAAACGTGCTGTATGAAAACCAGAAACTGATCGCCAATCAGTTTAACAGCGCCATCGGCAAAATCCAGGATAGCCTGTCCAGCACCGCCAGCGCCCTCGGCAAGCTGCAAGATGTGGTGAATCAAAATGCCCAAGCCCTGAACACACTGGTGAAGCAGCTGAGCAGCAACTTCGGCGCCATCAGCAGCGTGCTGAACGACATCCTGAGCAGACTGGACAAGGTGGAAGCCGAGGTGCAGATCGACAGACTGATCACAGGCAGACTGCAGTCCCTGCAGACCTACGTGACCCAGCAGTTGATTAGAGCCGCTGAGATTAGAGCCAGTGCCAACCTGGCTGCCACAAAGATGTCAGAATGCGTGCTGGGCCAGAGCAAGAGAGTGGACTTCTGCGGCAAAGGCTACCACCTGATGAGCTTTCCTCAGTCTGCACCCCACGGCGTGGTGTTTCTCCACGTGACATACGTGCCCGCGCAAGAAAAGAACTTTACAACCGCCCCAGCGATCTGCCACGACGGCAAGGCCCACTTCCCTCGGGAGGGTGTGTTCGTGAGCAATGGAACACACTGGTTCGTCACCCAGCGGAACTTCTACGAGCCTCAGATCATTACCACCGACAACACCTTCGTGAGCGGCAACTGTGACGTCGTTATCGGCATCGTGAACAATACCGTGTACGACCCCCTGCAGCCTGAGCTGGATAGCTTCAAAGAGGAACTGGACAAGTACTTCAAGAACCACACAAGCCCCGACGTGGACCTAGGCGACATCTCTGGAATCAACGCCAGCGTGGTGAACATCCAAAAGGAAATCGACAGACTGAACGAGGTGGCCAAGAATCTGAATGAAAGCCTGATCGATCTGCAGGAGCTGGGCAAGTACGAGCAGTACATCAAATGGCCTTGGTACATCTGGCTGGGCTTCATCGCTGGTCTGATCGCTATCGTGATGGTGACCATTATGCTGTGCTGCATGACCTCCTGCTGCTCTTGCCTGAAGGGCTGTTGTTCTTGCGGCTCTTGCTGCTGATGA SEQ ID NO:TAATACGACTCACTATAGGGACCAAACAGAGAATCCGTGAGTTACGATAAAAGGCGAAGG 18; NDV-AGCAATTGAAGTCGCACGGGTAGAAGGTGTGAATCTCGAGTGCGAGCCCGAAGCACAAAC HexaPro STCGAGAAAGCCTTCTGCCAACATGTCTTCCGTATTTGATGAGTACGAACAGCTCCTCGCG MolecularGCTCAGACTCGCCCCAATGGAGCTCATGGAGGGGGAGAAAAAGGGAGTACCTTAAAAGTA CloneGACGTCCCGGTATTCACTCTTAACAGTGATGACCCAGAAGATAGATGGAGCTTTGTGGTA AF077761.1_TTCTGCCTCCGGATTGCTGTTAGCGAAGATGCCAACAAACCACTCAGGCAAGGTGCTCTC LaSota_KanATATCTCTTTTATGCTCCCACTCACAGGTAATGAGGAACCATGTTGCCATTGCAGGGAAA R (withCAGAATGAAGCCACATTGGCCGTGCTTGAGATTGATGGCTTTGCCAACGGCACGCCCCAG stabilizingTTCAACAATAGGAGTGGAGTGTCTGAAGAGAGAGCACAGAGATTTGCGATGATAGCAGGA sequence inTCTCTCCCTCGGGCATGCAGCAACGGAACCCCGTTCGTCACAGCCGGGGCAGAAGATGAT L)GCACCAGAAGACATCACCGATACCCTGGAGAGGATCCTCTCTATCCAGGCTCAAGTATGGGTCACAGTAGCAAAAGCCATGACTGCGTATGAGACTGCAGATGAGTCGGAAACAAGGCGAATCAATAAGTATATGCAGCAAGGCAGGGTCCAAAAGAAATACATCCTCTACCCCGTATGCAGGAGCACAATCCAACTCACGATCAGACAGTCTCTTGCAGTCCGCATCTTTTTGGTTAGCGAGCTCAAGAGAGGCCGCAACACGGCAGGTGGTACCTCTACTTATTATAACCTGGTAGGGGACGTAGACTCATACATCAGGAATACCGGGCTTACTGCATTCTTCTTGACACTCAAGTACGGAATCAACACCAAGACATCAGCCCTTGCACTTAGTAGCCTCTCAGGCGACATCCAGAAGATGAAGCAGCTCATGCGTTTGTATCGGATGAAAGGAGATAATGCGCCGTACATGACATTACTTGGTGATAGTGACCAGATGAGCTTTGCGCCTGCCGAGTATGCACAACTTTACTCCTTTGCCATGGGTATGGCATCAGTCCTAGATAAAGGTACTGGGAAATACCAATTTGCCAGGGACTTTATGAGCACATCATTCTGGAGACTTGGAGTAGAGTACGCTCAGGCTCAGGGAAGTAGCATTAACGAGGATATGGCTGCCGAGCTAAAGCTAACCCCAGCAGCAATGAAGGGCCTGGCAGCTGCTGCCCAACGGGTCTCCGACGATACCAGCAGCATATACATGCCTACTCAACAAGTCGGAGTCCTCACTGGGCTTAGCGAGGGGGGGTCCCAAGCTCTACAAGGCGGATCGAATAGATCGCAAGGGCAACCAGAAGCCGGGGATGGGGAGACCCAATTCCTGGATCTGATGAGAGCGGTAGCAAATAGCATGAGGGAGGCGCCAAACTCTGCACAGGGCACTCCCCAATCGGGGCCTCCCCCAACTCCTGGGCCATCCCAAGATAACGACACCGACTGGGGGTATTGATGGACAAAACCCAGCCTGCTTCCACAAAAACATCCCAATGCCCTCACCCGTAGTCGACCCCTCGATTTGCGGCTCTATATGACCACACCCTCAAACAAACATCCCCCTCTTTCCTCCCTCCCCCTGCTGTACAACTCCGCACGCCCTAGATACCACAGGCACAATGCGGCTCACTAACAATCAAAACAGAGCCGAGGGAATTAGAAAAAAGTACGGGTAGAAGAGGGATATTCAGAGATCAGGGCAAGTCTCCCGAGTCTCTGCTCTCTCCTCTACCTGATAGACCAGGACAAACATGGCCACCTTTACAGATGCAGAGATCGACGAGCTATTTGAGACAAGTGGAACTGTCATTGACAACATAATTACAGCCCAGGGTAAACCAGCAGAGACTGTTGGAAGGAGTGCAATCCCACAAGGCAAGACCAAGGTGCTGAGCGCAGCATGGGAGAAGCATGGGAGCATCCAGCCACCGGCCAGTCAAGACAACCCCGATCGACAGGACAGATCTGACAAACAACCATCCACACCCGAGCAAACGACCCCGCATGACAGCCCGCCGGCCACATCCGCCGACCAGCCCCCCACCCAGGCCACAGACGAAGCCGTCGACACACAGTTCAGGACCGGAGCAAGCAACTCTCTGCTGTTGATGCTTGACAAGCTCAGCAATAAATCGTCCAATGCTAAAAAGGGCCCATGGTCGAGCCCCCAAGAGGGGAATCACCAACGTCCGACTCAACAGCAGGGGAGTCAACCCAGTCGCGGAAACAGTCAGGAAAGACCGCAGAACCAAGTCAAGGCCGCCCCTGGAAACCAGGGCACAGACGTGAACACAGCATATCATGGACAATGGGAGGAGTCACAACTATCAGCTGGTGCAACCCCTCATGCTCTCCGATCAAGGCAGAGCCAAGACAATACCCTTGTATCTGCGGATCATGTCCAGCCACCTGTAGACTTTGTGCAAGCGATGATGTCTATGATGGAGGCGATATCACAGAGAGTAAGTAAGGTTGACTATCAGCTAGATCTTGTCTTGAAACAGACATCCTCCATCCCTATGATGCGGTCCGAAATCCAACAGCTGAAAACATCTGTTGCAGTCATGGAAGCCAACTTGGGAATGATGAAGATTCTGGATCCCGGTTGTGCCAACATTTCATCTCTGAGTGATCTACGGGCAGTTGCCCGATCTCACCCGGTTTTAGTTTCAGGCCCTGGAGACCCCTCTCCCTATGTGACACAAGGAGGCGAAATGGCACTTAATAAACTTTCGCAACCAGTGCCACATCCATCTGAATTGATTAAACCCGCCACTGCATGCGGGCCTGATATAGGAGTGGAAAAGGACACTGTCCGTGCATTGATCATGTCACGCCCAATGCACCCGAGTTCTTCAGCCAAGCTCCTAAGCAAGTTAGATGCAGCCGGGTCGATCGAGGAAATCAGGAAAATCAAGCGCCTTGCTCTAAATGGCTAATTACTACTGCCACACGTAGCGGGTCCCTGTCCACTCGGCATCACACGGAATCTGCACCGAGTTCCCCCTCTAGATTAGAAAAAATACGGGTAGAACCGCCACCATGTTCGTGTTCCTGGTCCTGCTGCCACTGGTAAGCTCCCAATGTGTAAACTTAACCACAAGAACCCAGCTCCCACCTGCCTACACCAACAGCTTCACCAGAGGCGTTTATTACCCCGACAAGGTATTCCGGTCTTCTGTTCTGCACTCTACCCAGGACCTGTTTCTGCCCTTTTTCAGCAACGTGACATGGTTCCACGCCATCCACGTGTCTGGCACAAACGGCACCAAGCGGTTTGATAATCCTGTGCTCCCTTTCAATGACGGCGTGTACTTCGCCTCTACTGAGAAGAGCAACATCATCCGGGGCTGGATCTTTGGCACAACACTGGACTCTAAAACCCAGAGCCTGCTGATCGTGAACAACGCCACCAACGTGGTGATTAAGGTGTGCGAGTTCCAGTTCTGCAATGACCCTTTCCTCGGCGTGTACTACCACAAGAACAACAAAAGTTGGATGGAAAGCGAATTCAGGGTGTACTCAAGCGCCAACAACTGTACCTTCGAGTACGTGAGCCAGCCTTTCCTGATGGACCTAGAAGGTAAGCAGGGCAATTTCAAGAACCTCAGAGAGTTCGTGTTCAAGAATATTGACGGCTACTTCAAAATCTACAGCAAGCACACCCCAATCAACCTGGTGCGGGACCTGCCCCAGGGCTTTAGCGCGCTGGAGCCTCTGGTGGACCTGCCTATCGGCATCAACATCACCCGGTTCCAGACACTGCTGGCTCTGCATAGAAGCTACCTGACACCTGGCGACAGTTCTTCTGGCTGGACAGCCGGCGCCGCCGCCTACTACGTGGGCTACCTGCAGCCTAGAACATTCCTGCTGAAATACAACGAGAACGGCACGATCACAGACGCCGTGGACTGCGCCCTGGATCCCCTGTCTGAGACAAAGTGCACCCTGAAGTCTTTCACCGTGGAGAAGGGCATCTACCAGACCTCCAACTTCAGAGTGCAGCCTACCGAATCCATCGTGCGCTTTCCCAACATCACCAACCTGTGCCCCTTCGGCGAGGTCTTTAATGCCACGAGATTCGCCAGCGTGTATGCCTGGAACAGAAAGAGAATCAGCAACTGCGTGGCCGACTACAGCGTGCTGTACAACAGCGCCTCTTTCAGCACATTTAAGTGCTACGGAGTGTCTCCTACCAAACTCAACGATCTGTGCTTCACGAACGTGTATGCCGACAGCTTCGTGATCCGAGGAGATGAGGTGCGGCAGATCGCTCCAGGACAGACAGGCAAGATCGCCGACTACAACTACAAGCTGCCCGACGACTTTACCGGCTGCGTGATCGCTTGGAACAGCAATAACCTGGACTCAAAGGTTGGAGGAAACTACAACTACCTGTACAGACTGTTCAGAAAGTCCAACCTGAAGCCCTTCGAGAGAGACATCTCTACAGAAATCTACCAGGCCGGCAGCACCCCATGTAACGGCGTGGAAGGCTTCAACTGCTACTTCCCTCTGCAGTCTTATGGCTTCCAGCCCACAAACGGAGTGGGCTATCAGCCTTACCGCGTGGTTGTCCTGAGCTTTGAGCTGCTGCATGCCCCTGCTACGGTGTGTGGACCTAAGAAGTCCACCAACCTGGTGAAGAACAAGTGTGTGAACTTCAACTTCAACGGCCTGACCGGCACCGGGGTGCTGACAGAGTCTAACAAGAAATTCCTGCCATTCCAGCAATTCGGCCGGGACATCGCCGACACCACCGACGCCGTGCGGGATCCTCAGACCCTCGAAATCCTGGACATCACCCCCTGTAGCTTCGGCGGCGTGAGCGTGATCACCCCTGGCACAAACACCAGCAATCAAGTGGCTGTCCTGTACCAGGATGTCAATTGCACAGAAGTGCCTGTGGCCATCCACGCCGATCAGCTGACCCCCACCTGGCGGGTGTACTCGACAGGAAGCAACGTGTTTCAAACAAGAGCCGGCTGCCTGATCGGGGCCGAGCACGTGAACAATTCCTACGAGTGCGACATCCCCATCGGCGCCGGCATCTGTGCCTCTTACCAGACACAGACCAATTCCCCTggtagtgcaagtTCCGTGGCCAGCCAGAGCATCATCGCCTACACCATGAGCCTGGGCGCCGAAAACAGCGTTGCATATTCCAACAACAGCATCGCCATCCCTACCAACTTCACCATCAGCGTGACCACAGAAATCCTGCCTGTGTCCATGACCAAGACAAGCGTTGATTGCACCATGTACATCTGCGGCGATAGCACAGAGTGCAGCAATCTGCTGCTGCAGTACGGTAGCTTCTGCACCCAGCTGAATAGAGCCCTGACCGGCATCGCTGTGGAACAGGACAAAAACACCCAGGAGGTCTTCGCCCAGGTGAAGCAAATCTACAAGACCCCTCCAATCAAGGACTTCGGAGGCTTTAACTTTAGCCAGATCCTGCCTGATCCCTCCAAGCCTAGCAAACGGAGTcctATCGAGGACCTGCTCTTCAACAAGGTGACCCTGGCTGACGCCGGCTTCATTAAGCAGTACGGCGATTGCCTCGGCGACATCGCTGCAAGAGACCTGATCTGCGCCCAGAAGTTCAACGGCCTGACCGTGCTGCCTCCTCTCCTGACAGACGAGATGATCGCCCAGTACACCTCTGCCCTTCTGGCTGGCACCATCACCAGCGGATGGACCTTTGGAGCCGGAcctGCCCTGCAGATCCCTTTCcctATGCAGATGGCCTACAGATTCAACGGGATCGGAGTGACCCAAAACGTGCTGTATGAAAACCAGAAACTGATCGCCAATCAGTTTAACAGCGCCATCGGCAAAATCCAGGATAGCCTGTCCAGCACCccaAGCGCCCTCGGCAAGCTGCAAGATGTGGTGAATCAAAATGCCCAAGCCCTGAACACACTGGTGAAGCAGCTGAGCAGCAACTTCGGCGCCATCAGCAGCGTGCTGAACGACATCCTGAGCAGACTGGACccacctGAAGCCGAGGTGCAGATCGACAGACTGATCACAGGCAGACTGCAGTCCCTGCAGACCTACGTGACCCAGCAGTTGATTAGAGCCGCTGAGATTAGAGCCAGTGCCAACCTGGCTGCCACAAAGATGTCAGAATGCGTGCTGGGCCAGAGCAAGAGAGTGGACTTCTGCGGCAAAGGCTACCACCTGATGAGCTTTCCTCAGTCTGCACCCCACGGCGTGGTGTTTCTCCACGTGACATACGTGCCCGCGCAAGAAAAGAACTTTACAACCGCCCCAGCGATCTGCCACGACGGCAAGGCCCACTTCCCTCGGGAGGGTGTGTTCGTGAGCAATGGAACACACTGGTTCGTCACCCAGCGGAACTTCTACGAGCCTCAGATCATTACCACCGACAACACCTTCGTGAGCGGCAACTGTGACGTCGTTATCGGCATCGTGAACAATACCGTGTACGACCCCCTGCAGCCTGAGCTGGATAGCTTCAAAGAGGAACTGGACAAGTACTTCAAGAACCACACAAGCCCCGACGTGGACCTAGgcgacATCTCTGGAATCAACGCCAGCGTGGTGAACATCCAAAAGGAAATCGACAGACTGAACGAGGTGGCCAAGAATCTGAATGAAAGCCTGATCGATCTGCAGGAGCTGGGCAAGTACGAGCAGTACATCAAATGGCCTTGGTACATCTGGCTGGGCTTCATCGCTGGTCTGATCGCTATCGTGATGGTGACCATTATGCTGTGCTGCATGACCTCCTGCTGCTCTTGCCTGAAGGGCTGTTGTTCTTGCGGCTCTTGCTGCAAGTTCGACGAGGATGACTCTGAACCTGTTCTGAAGGGCgtgaagctgcactacacctgataaacgcgtACCCAAGGTCCAACTCTCCAAGCGGCAATCCTCTCTCGCTTCCTCAGCCCCACTGAATGGTCGCGTAACCGTAATTAATCTAGCTACATTTAAGATTAAGAAAAAATACGGGTAGAATTGGAGTGCCCCAATTGTGCCAAGATGGACTCATCTAGGACAATTGGGCTGTACTTTGATTCTGCCCATTCTTCTAGCAACCTGTTAGCATTTCCGATCGTCCTACAAGGCACAGGAGATGGGAAGAAGCAAATCGCCCCGCAATATAGGATCCAGCGCCTTGACTTGTGGACTGATAGTAAGGAGGACTCAGTATTCATCACCACCTATGGATTCATCTTTCAAGTTGGGAATGAAGAAGCCACTGTCGGCATGATCGATGATAAACCCAAGCGCGAGTTACTTTCCGCTGCGATGCTCTGCCTAGGAAGCGTCCCAAATACCGGAGACCTTATTGAGCTGGCAAGGGCCTGTCTCACTATGATAGTCACATGCAAGAAGAGTGCAACTAATACTGAGAGAATGGTTTTCTGAGTAGTGCAGGCACCCCAAGTGCTGCAAAGCTGTAGGGTTGTGGCAAACAAATACTCATCAGTGAATGCAGTCAAGCACGTGAAAGCGCCAGAGAAGATTCCCGGGAGTGGAACCCTAGAATACAAGGTGAACTTTGTCTCCTTGACTGTGGTACCGAAGAAGGATGTCTACAAGATCCCAGCTGCAGTATTGAAGGTTTCTGGCTCGAGTCTGTACAATCTTGCGCTCAATGTCACTATTAATGTGGAGGTAGACCCGAGGAGTCCTTTGGTTAAATCTTTGTCTAAGTCTGACAGCGGATACTATGCTAACCTCTTCTTGCATATTGGACTTATGACCACCGTAGATAGGAAGGGGAAGAAAGTGACATTTGACAAGCTGGAAAAGAAAATAAGGAGCCTTGATCTATCTGTCGGGCTCAGTGATGTGCTCGGGCCTTCCGTGTTGGTAAAAGCAAGAGGTGCACGGACTAAGCTTTTGGCACCTTTCTTCTCTAGCAGTGGGACAGCCTGCTATCCCATAGCAAATGCTTCTCCTCAGGTGGCCAAGATACTCTGGAGTCAAACCGCGTGCCTGCGGAGCGTTAAAATCATTATCCAAGCAGGTACCCAACGCGCTGTCGCAGTGACCGCCGACCACGAGGTTACCTCTACTAAGCTGGAGAAGGGGCACACCCTTGCCAAATACAATCCTTTTAAGAAATAAGCTGCGTCTCTGAGATTGCGCTCCGCCCACTCACCCAGATCATCATGACACAAAAAACTAATCTGTCTTGATTATTTACAGTTAGTTTACCTGTCTATCAAGTTAGAAAAAACACGGGTAGAAGATTCTGGATCCCGGTTGGCGCCCTCCAGGTGCAAGttaattaaATGGGCTCCAGACCTTCTACCAAGAACCCAGCACCTATGATGCTGACTATCCGGGTTGCGCTGGTACTGAGTTGCATCTGTCCGGCAAACTCCATTGATGGCAGGCCTCTTGCAGCTGCAGGAATTGTGGTTACAGGAGACAAAGCCGTCAACATATACACCTCATCCCAGACAGGATCAATCATAGTTAAGCTCCTCCCGAATCTGCCCAAGGATAAGGAGGCATGTGCGAAAGCCCCCTTGGATGCATACAACAGGACATTGACCACTTTGCTCACCCCCCTTGGTGACTCTATCCGTAGGATACAAGAGTCTGTGACTACATCTGGAGGGGGGAGACAGGGGCGCCTTATAGGCGCCATTATTGGCGGTGTGGCTCTTGGGGTTGCAACTGCCGCACAAATAACAGCGGCCGCAGCTCTGATACAAGCCAAACAAAATGCTGCCAACATCCTCCGACTTAAAGAGAGCATTGCCGCAACCAATGAGGCTGTGCATGAGGTCACTGACGGATTATCGCAACTAGCAGTGGCAGTTGGGAAGATGCAGCAGTTTGTTAATGACCAATTTAATAAAACAGCTCAGGAATTAGACTGCATCAAAATTGCACAGCAAGTTGGTGTAGAGCTCAACCTGTACCTAACCGAATTGACTACAGTATTCGGACCACAAATCACTTCACCTGCTTTAAACAAGCTGACTATTCAGGCACTTTACAATCTAGCTGGTGGAAATATGGATTACTTATTGACTAAGTTAGGTGTAGGGAACAATCAACTCAGCTCATTAATCGGTAGCGGCTTAATCACtGGcAACCCTATTCTATACGACTCACAGACTCAACTCTTGGGTATACAGGTAACTgcaCCTTCAGTCGGGAACCTAAATAATATGCGTGCCACCTACTTGGAAACCTTATCCGTAAGCACAACCAGGGGATTTGCCTCGGCACTTGTCCCCAAAGTGGTGACACAGGTCGGTTCTGTGATAGAAGAACTTGACACCTCATACTGTATAGAAACTGACTTAGATTTATATTGTACAAGAATAGTAACGTTCCCTATGTCCCCTGGTATTTATTCCTGCTTGAGCGGCAATACGTCGGCCTGTATGTACTCAAAGACCGAAGGCGCACTTACTACACCATACATGACTATCAAAGGTTCAGTCATCGCCAACTGCAAGATGACAACATGTAGATGTGTAAACCCCCCGGGTATCATATCGCAAAACTATGGAGAAGCCGTGTCTCTAATAGATAAACAATCATGCAATGTTTTATCCTTAGGCGGGATAACTTTAAGGCTCAGTGGGGAATTCGATGTAACTTATCAGAAGAATATCTCAATACAAGATTCTCAAGTAATAATAACAGGCAATCTTGATATCTCAACTGAGCTTGGGAATGTCAACAACTCGATCAGTAATGCTTTGAATAAGTTAGAGGAAAGCAACAGAAAACTAGACAAAGTCAATGTCAAACTGACTAGCACATCTGCTCTCATTACgTATATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTGATTCTAGCATGCTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTTATTATGGCTTGGGAATAATACaCTcGATCAGATGAGAGCCACTACAAAAATGTGAACACAGATGAGGAACGAAGGTTTCCCTAATAGTAATTTGTGTGAAAGTTCTGGTAGTCTGTCAGTTCAGAGAGTTAAGAAAAAACTACCGGTTGTAGATGACCAAAGGACGATATACGGGTAGAACGGTAAGAGAGGCCGCCCCTCAATTGCGAGCCAGGCTTCACAACCTCCGTTCTACCGCTTCACCGACAACAGTCCTCAATCATGGACCGCGCCGTTAGCCAAGTTGCGTTAGAGAATGATGAAAGAGAGGCAAAAAATACATGGCGCTTGATATTCCGGATTGCAATCTTATTCTTAACAGTAGTGACCTTGGCTATATCTGTAGCCTCCCTTTTATATAGCATGGGGGCTAGCACACCTAGCGATCTTGTAGGCATACCGACTAGGATTTCCAGGGCAGAAGAAAAGATTACATCTACACTTGGTTCCAATCAAGATGTAGTAGATAGGATATATAAGCAAGTGGCCCTTGAGTCTCCGTTGGCATTGTTAAATACTGAGACCACAATTATGAACGCAATAACATCTCTCTCTTATCAGATTAATGGAGCTGCAAACAACAGTGGGTGGGGGGCACCTATCCATGACCCAGATTATATAGGGGGGATAGGCAAAGAACTCATTGTAGATGATGCTAGTGATGTCACATCATTCTATCCCTCTGCATTTCAAGAACATCTGAATTTTATCCCGGCGCCTACTACAGGATCAGGTTGCACTCGAATACCCTCATTTGACATGAGTGCTACCCATTACTGCTACACCCATAATGTAATATTGTCTGGATGCAGAGATCACTCACATTCATATCAGTATTTAGCACTTGGTGTGCTCCGGACATCTGCAACAGGGAGGGTATTCTTTTCTACTCTGCGTTCCATCAACCTGGACGACACCCAAAATCGGAAGTCTTGCAGTGTGAGTGCAACTCCCCTGGGTTGTGATATGCTGTGCTCGAAAGTCACGGAGACAGAGGAAGAAGATTATAACTCAGCTGTCCCTACGCGGATGGTACATGGGAGGTTAGGGTTCGACGGCCAGTACCACGAAAAGGACCTAGATGTCACAACATTATTCGGGGACTGGGTGGCCAACTACCCAGGAGTAGGGGGTGGATCTTTTATTGACAGCCGCGTATGGTTCTCAGTCTACGGAGGGTTAAAACCCAATTCACCCAGTGACACTGTACAGGAAGGGAAATATGTGATATACAAGCGATACAATGACACATGCCCAGATGAGCAAGACTACCAGATTCGAATGGCCAAGTCTTCGTATAAGCCTGGACGGTTTGGTGGGAAACGCATACAGCAGGCTATCTTATCTATCAAGGTGTCAACATCCTTAGGCGAAGACCCGGTACTGACTGTACCGCCCAACACAGTCACACTCATGGGGGCCGAAGGCAGAATTCTCACAGTAGGGACATCTCATTTCTTGTATCAACGAGGGTCATCATACTTCTCTCCCGCGTTATTATATCCTATGACAGTCAGCAACAAAACAGCCACTCTTCATAGTCCTTATACATTCAATGCCTTCACTCGGCCAGGTAGTATCCCTTGCCAGGCTTCAGCAAGATGCCCCAACTCGTGTGTTACTGGAGTCTATACAGATCCATATCCCCTAATCTTCTATAGAAACCACACCTTGCGAGGGGTATTCGGGACAATGCTTGATGGTGTACAAGCAAGACTTAACCCTGCGTCTGCAGTATTCGATAGCACATCCCGCAGTCGCATTACTCGAGTGAGTTCAAGCAGTACCAAAGCAGCATACACAACATCAACTTGTTTTAAAGTGGTCAAGACTAATAAGACCTATTGTCTCAGCATTGCTGAAATATCTAATACTCTCTTCGGAGAATTCAGAATCGTCCCGTTACTAGTTGAGATCCTCAAAGATGACGGGGTTAGAGAAGCCAGGTCTGGCTAGggcgcgccTTGAGTCAATTATAAAGGAGTTGGAAAGATGGCATTGTATCACCTATCTTCTGCGACATCAAGAATCAAACCGAATGCCGGCGCGTGCTCGAATTCCATGTTGCCAGTTGACCACAATCAGCCAGTGCTCATGCGATCAGATTAAGCCTTGTCATTAATCTCTTGATTAAGAAAAAATGTAAGTGGCAATGAGATACAAGGCAAAACAGCTCATGGTAAATAATACGGGTAGGACATGGCGAGCTCCGGTCCTGAAAGGGCAGAGCATCAGATTATCCTACCAGAGCCACACCTGTCTTCACCATTGGTCAAGCACAAACTACTCTATTACTGGAAATTAACTGGGCTACCGCTTCCTGATGAATGTGACTTCGACCACCTCATTCTCAGCCGACAATGGAAAAAAATACTTGAATCGGCCTCTCCTGATACTGAGAGAATGATAAAACTCGGAAGGGCAGTACACCAAACTCTTAACCACAATTCCAGAATAACCGGAGTGCTCCACCCCAGGTGTTTAGAACAACTGGCTAATATTGAGGTCCCAGATTCAACCAACAAATTTCGGAAGATTGAGAAGAAGATCCAAATTCACAACACGAGATATGGAGAACTGTTCACAAGGCTGTGTACGCATATAGAGAAGAAACTGCTGGGGTCATCTTGGTCTAACAATGTCCCCCGGTCAGAGGAGTTCAGCAGCATTCGTACGGATCCGGCATTCTGGTTTCACTCAAAATGGTCCACAGCCAAGTTTGCATGGCTCCATATAAAACAGATCCAGAGGCATCTGATGGTGGCAGCTAAGACAAGGTCTGCGGCCAACAAATTGGTGATGCTAACCCATAAGGTAGGCCAAGTCTTTGTCACTCCTGAACTTGTCGTTGTGACGCATACGAATGAGAACAAGTTCACATGTCTTACCCAGGAACTTGTATTGATGTATGCAGATATGATGGAGGGCAGAGATATGGTCAACATAATATCAACCACGGCGGTGCATCTCAGAAGCTTATCAGAGAAAATTGATGACATTTTGCGGTTAATAGACGCTCTGGCAAAAGACTTGGGTAATCAAGTCTACGATGTTGTATCACTAATGGAGGGATTTGCATACGGAGCTGTCCAGCTACTCGAGCCGTCAGGTACATTTGCAGGAGATTTCTTCGCATTCAACCTGCAGGAGCTTAAAGACATTCTAATTGGCCTCCTCCCCAATGATATAGCAGAATCCGTGACTCATGCAATCGCTACTGTATTCTCTGGTTTAGAACAGAATCAAGCAGCTGAGATGTTGTGTCTGTTGCGTCTGTGGGGTCACCCACTGCTTGAGTCCCGTATTGCAGCAAAGGCAGTCAGGAGCCAAATGTGCGCACCGAAAATGGTAGACTTTGATATGATCCTTCAGGTACTGTCTTTCTTCAAGGGAACAATCATCAACGGGTACAGAAAGAAGAATGCAGGTGTGTGGCCGCGAGTCAAAGTGGATACAATATATGGGAAGGTCATTGGGCAACTACATGCAGATTCAGCAGAGATTTCACACGATATCATGTTGAGAGAGTATAAGAGTTTATCTGCACTTGAATTTGAGCCATGTATAGAATATGACCCTGTCACCAACCTGAGCATGTTCCTAAAAGACAAGGCAATCGCACACCCCAACGATAATTGGCTTGCCTCGTTTAGGCGGAACCTTCTCTCCGAAGACCAGAAGAAACATGTAAAAGAAGCAACTTCGACTAATCGCCTCTTGATAGAGTTTTTAGAGTCAAATGATTTTGATCCATATAAAGAGATGGAATATCTGACGACCCTTGAGTACCTTAGAGATGACAATGTGGCAGTATCATACTCGCTCAAGGAGAAGGAAGTGAAAGTTAATGGACGGATCTTCGCTAAGCTGACAAAGAAGTTAAGGAACTGTCAGGTGATGGCGGAAGGGATCCTAGCCGATCAGATTGCACCTTTCTTTCAGGGAAATGGAGTCATTCAGGATAGCATATCCTTGACCAAGAGTATGCTAGCGATGAGTCAACTGTCTTTTAACAGCAATAAGAAACGTATCACTGACTGTAAAGAAAGAGTATCTTCAAACCGCAATCATGATCCGAAAAGCAAGAACCGTCGGAGAGTTGCAACCTTCATAACAACTGACCTGCAAAAGTACTGTCTTAATTGGAGATATCAGACAATCAAATTGTTCGCTCATGCCATCAATCAGTTGATGGGCCTACCTCACTTCTTCGAATGGATTCACCTAAGACTGATGGACACTACGATGTTCGTAGGAGACCCTTTCAATCCTCCAAGTGACCCTACTGACTGTGACCTCTCAAGAGTCCCTAATGATGACATATATATTGTCAGTGCCAGAGGGGGTATCGAAGGATTATGCCAGAAGCTATGGACAATGATCTCAATTGCTGCAATCCAACTTGCTGCAGCTAGATCGCATTGTCGTGTTGCCTGTATGGTACAGGGTGATAATCAAGTAATAGCAGTAACGAGAGAGGTAAGATCAGACGACTCTCCGGAGATGGTGTTGACACAGTTGCATCAAGCCAGTGATAATTTCTTCAAGGAATTAATTCATGTCAATCATTTGATTGGCCATAATTTGAAGGATCGTGAAACCATCAGGTCAGACACATTCTTCATATACAGCAAACGAATCTTCAAAGATGGAGCAATCCTCAGTCAAGTCCTCAAAAATTCATCTAAATTAGTGCTAGTGTCAGGTGATCTCAGTGAAAACACCGTAATGTCCTGTGCCAACATTGCCTCTACTGTAGCACGGCTATGCGAGAACGGGCTTCCCAAAGACTTCTGTTACTATTTAAACTATATAATGAGTTGTGTGCAGACATACTTTGACTCTGAGTTCTCCATCACCAACAATTCGCACCCCGATCTTAATCAGTCGTGGATTGAGGACATCTCTTTTGTGCACTCATATGTTCTGACTCCTGCCCAATTAGGGGGACTGAGTAACCTTCAATACTCAAGGCTCTACACTAGAAATATCGGTGACCCGGGGACTACTGCTTTTGCAGAGATCAAGCGACTAGAAGCAGTGGGATTACTGAGTCCTAACATTATGACTAATATCTTAACTAGGCCGCCTGGGAATGGAGATTGGGCCAGTCTGTGCAACGACCCATACTCTTTCAATTTTGAGACTGTTGCAAGCCCAAATATTGTTCTTAAGAAACATACGCAAAGAGTCCTATTTGAAACTTGTTCAAATCCCTTATTGTCTGGAGTGCACACAGAGGATAATGAGGCAGAAGAGAAGGCATTGGCTGAATTCTTGCTTAATCAAGAGGTGATTCATCCCCGCGTTGCGCATGCCATCATGGAGGCAAGCTCTGTAGGTAGGAGAAAGCAAATTCAAGGGCTTGTTGACACAACAAACACCGTAATTAAGATTGCGCTTACTAGGAGGCCATTAGGCATCAAGAGGCTGATGCGGATAGTCAATTATTCTAGCATGCATGCAATGCTGTTTAGAGACGATGTTTTTTCCTCCAGTAGATCCAACCACCCCTTAGTCTCTTCTAATATGTGTTCTCTGACACTGGCAGACTATGCACGGAATAGAAGCTGGTCACCTTTGACGGGAGGCAGGAAAATACTGGGTGTATCTAATCCTGATACGATAGAACTCGTAGAGGGTGAGATTCTTAGTGTAAGCGGAGGGTGTACAAGATGTGACAGCGGAGATGAACAATTTACTTGGTTCCATCTTCCAAGCAATATAGAATTGACCGATGACACCAGCAAGAATCCTCCGATGAGGGTACCATATCTCGGGTCAAAGACACAGGAGAGGAGAGCTGCCTCACTTGCAAAAATAGCTCATATGTCGCCACATGTAAAGGCTGCCCTAAGGGCATCATCCGTGTTGATCTGGGCTTATGGGGATAATGAAGTAAATTGGACTGCTGCTCTTACGATTGCAAAATCTCGGTGTAATGTAAACTTAGAGTATCTTCGGTTACTGTCCCCTTTACCCACGGCTGGGAATCTTCAACATAGACTAGATGATGGTATAACTCAGATGACATTCACCCCTGCATCTCTCTACAGGgtgtcaccttacattcacatatccaatgattctcaaaggctgttcactgaagaaggagtcaaagaggggaatgtggtttaccaacagatcATGCTCTTGGGTTTATCTCTAATCGAATCGATCTTTCCAATGACAACAACCAGGACATATGATGAGATCACACTGCACCTACATAGTAAATTTAGTTGCTGTATCAGAGAAGCACCTGTTGCGGTTCCTTTCGAGCTACTTGGGGTGGTACCGGAACTGAGGACAGTGACCTCAAATAAGTTTATGTATGATCCTAGCCCTGTATCGGAGGGAGACTTTGCGAGACTTGACTTAGCTATCTTCAAGAGTTATGAGCTTAATCTGGAGTCATATCCCACGATAGAGCTAATGAACATTCTTTCAATATCCAGCGGGAAGTTGATTGGCCAGTCTGTGGTTTCTTATGATGAAGATACCTCCATAAAGAATGACGCCATAATAGTGTATGACAATACCCGAAATTGGATCAGTGAAGCTCAGAATTCAGATGTGGTCCGCCTATTTGAATATGCAGCACTTGAAGTGCTCCTCGACTGTTCTTACCAACTCTATTACCTGAGAGTAAGAGGCCTAGACAATATTGTCTTATATATGGGTGATTTATACAAGAATATGCCAGGAATTCTACTTTCCAACATTGCAGCTACAATATCTCATCCCGTCATTCATTCAAGGTTACATGCAGTGGGCCTGGTCAACCATGACGGATCACACCAACTTGCAGATACGGATTTTATCGAAATGTCTGCAAAACTATTAGTATCTTGCACCCGACGTGTGATCTCCGGCTTATATTCAGGAAATAAGTATGATCTGCTGTTCCCATCTGTCTTAGATGATAACCTGAATGAGAAGATGCTTCAGCTGATATCCCGGTTATGCTGTCTGTACACGGTACTCTTTGCTACAACAAGAGAAATCCCGAAAATAAGAGGCTTAACTGCAGAAGAGAAATGTTCAATACTCACTGAGTATTTACTGTCGGATGCTGTGAAACCATTACTTAGCCCCGATCAAGTGAGCTCTATCATGTCTCCTAACATAATTACATTCCCAGCTAATCTGTACTACATGTCTCGGAAGAGCCTCAATTTGATCAGGGAAAGGGAGGACAGGGATACTATCCTGGCGTTGTTGTTCCCCCAAGAGCCATTATTAGAGTTCCCTTCTGTGCAAGATATTGGTGCTCGAGTGAAAGATCCATTCACCCGACAACCTGCGGCATTTTTGCAAGAGTTAGATTTGAGTGCTCCAGCAAGGTATGACGCATTCACACTTAGTCAGATTCATCCTGAACTCACATCTCCAAATCCGGAGGAAGACTACTTAGTACGATACTTGTTCAGAGGGATAGGGACTGCATCTTCCTCTTGGTATAAGGCATCTCATCTCCTTTCTGTACCCGAGGTAAGATGTGCAAGACACGGGAACTCCTTATACTTAGCTGAAGGGAGCGGAGCCATCATGAGTCTTCTCGAACTGCATGTACCACATGAAACTATCTATTACAATACGCTCTTTTCAAATGAGATGAACCCCCCGCAACGACATTTCGGGCCGACCCCAACTCAGTTTTTGAATTCGGTTGTTTATAGGAATCTACAGGCGGAGGTAACATGCAAAGATGGATTTGTCCAAGAGTTCCGTCCATTATGGAGAGAAAATACAGAGGAAAGTGACCTGACCTCAGATAAAGCAGTGGGGTATATTACATCTGCAGTGCCCTACAGATCTGTATCATTGCTGCATTGTGACATTGAAATTCCTCCAGGGTCCAATCAAAGCTTACTAGATCAACTAGCTATCAATTTATCTCTGATTGCCATGCATTCTGTAAGGGAGGGCGGGGTAGTAATCATCAAAGTGTTGTATGCAATGGGATACTACTTTCATCTACTCATGAACTTGTTTGCTCCGTGTTCCACAAAAGGATATATTCTCTCTAATGGTTATGCATGTCGAGGAGATATGGAGTGTTACCTGGTATTTGTCATGGGTTACCTGGGCGGGCCTACATTTGTACATGAGGTGGTGAGGATGGCAAAAACTCTGGTGCAGCGGCACGGTACGCTCTTGTCTAAATCAGATGAGATCACACTGACCAGGTTATTCACCTCACAGCGGCAGCGTGTGACAGACATCCTATCCAGTCCTTTACCAAGATTAATAAAGTACTTGAGGAAGAATATTGACACTGCGCTGATTGAAGCCGGGGGACAGCCCGTCCGTCCATTCTGTGCGGAGAGTCTGGTGAGCACGCTAGCGAACATAACTCAGATAACCCAGATTATCGCTAGTCACATTGACACAGTTATCCGGTCTGTGATATATATGGAAGCTGAGGGTGATCTCGCTGACACAGTATTTCTATTTACCCCTTACAATCTCTCTACTGACGGGAAAAAGAGGACATCACTTATACAGTGCACGAGACAGATCCTAGAGGTTACAATACTAGGTCTTAGAGTCGAAAATCTCAATAAAATAGGCGATATAATCAGCCTAGTGCTTAAAGGCATGATCTCCATGGAGGACCTTATCCCACTAAGGACATACTTGAAGCATAGTACCTGCCCTAAATATTTGAAGGCTGTCCTAGGTATTACCAAACTCAAAGAAATGTTTACAGACACTTCTGTATTGTACTTGACTCGTGCTCAACAAAAATTCTACATGAAAACTATAGGCAATGCAGTCAAAGGATATTACAGTAACTGTGACTCTTAACGAAAATCACATATTAATAGGCTCCTTTTTTGGCCAATTGTATTCTTGTTGATTTAATCATATTATGTTAGAAAAAAGTTGAACCCTGACTCCTTAGGACTCGAATTCGAACTCAAATAAATGTCTTAAAAAAAGGTTGCGCACAATTATTCTTGAGTGTAGTCTCGTCATTCACCAAATCTTTGTTTGGTGGCCGGCATGGTCCCAGCCTCCTCGCTGGCGCCGGCTGGGCAACATTCCGAGGGGACCGTCCCCTCGGTAATGGCGAATGGGACGTCGACTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTATA SEQ ID NO:TAATACGACTCACTATAGGGACCAAACAGAGAATCCGTGAGTTACGATAAAAGGCGAAGG 19; NDV-AGCAATTGAAGTCGCACGGGTAGAAGGTGTGAATCTCGAGTGCGAGCCCGAAGCACAAAC FLS-6PTCGAGAAAGCCTTCTGCCAACATGTCTTCCGTATTTGATGAGTACGAACAGCTCCTCGCG MolecularGCTCAGACTCGCCCCAATGGAGCTCATGGAGGGGGAGAAAAAGGGAGTACCTTAAAAGTA CloneGACGTCCCGGTATTCACTCTTAACAGTGATGACCCAGAAGATAGATGGAGCTTTGTGGTA AF077761.1_TTCTGCCTCCGGATTGCTGTTAGCGAAGATGCCAACAAACCACTCAGGCAAGGTGCTCTC LaSota_KanATATCTCTTTTATGCTCCCACTCACAGGTAATGAGGAACCATGTTGCCATTGCAGGGAAA R (withCAGAATGAAGCCACATTGGCCGTGCTTGAGATTGATGGCTTTGCCAACGGCACGCCCCAG stabilizingTTCAACAATAGGAGTGGAGTGTCTGAAGAGAGAGCACAGAGATTTGCGATGATAGCAGGA sequence inTCTCTCCCTCGGGCATGCAGCAACGGAACCCCGTTCGTCACAGCCGGGGCAGAAGATGAT L)GCACCAGAAGACATCACCGATACCCTGGAGAGGATCCTCTCTATCCAGGCTCAAGTATGGGTCACAGTAGCAAAAGCCATGACTGCGTATGAGACTGCAGATGAGTCGGAAACAAGGCGAATCAATAAGTATATGCAGCAAGGCAGGGTCCAAAAGAAATACATCCTCTACCCCGTATGCAGGAGCACAATCCAACTCACGATCAGACAGTCTCTTGCAGTCCGCATCTTTTTGGTTAGCGAGCTCAAGAGAGGCCGCAACACGGCAGGTGGTACCTCTACTTATTATAACCTGGTAGGGGACGTAGACTCATACATCAGGAATACCGGGCTTACTGCATTCTTCTTGACACTCAAGTACGGAATCAACACCAAGACATCAGCCCTTGCACTTAGTAGCCTCTCAGGCGACATCCAGAAGATGAAGCAGCTCATGCGTTTGTATCGGATGAAAGGAGATAATGCGCCGTACATGACATTACTTGGTGATAGTGACCAGATGAGCTTTGCGCCTGCCGAGTATGCACAACTTTACTCCTTTGCCATGGGTATGGCATCAGTCCTAGATAAAGGTACTGGGAAATACCAATTTGCCAGGGACTTTATGAGCACATCATTCTGGAGACTTGGAGTAGAGTACGCTCAGGCTCAGGGAAGTAGCATTAACGAGGATATGGCTGCCGAGCTAAAGCTAACCCCAGCAGCAATGAAGGGCCTGGCAGCTGCTGCCCAACGGGTCTCCGACGATACCAGCAGCATATACATGCCTACTCAACAAGTCGGAGTCCTCACTGGGCTTAGCGAGGGGGGGTCCCAAGCTCTACAAGGCGGATCGAATAGATCGCAAGGGCAACCAGAAGCCGGGGATGGGGAGACCCAATTCCTGGATCTGATGAGAGCGGTAGCAAATAGCATGAGGGAGGCGCCAAACTCTGCACAGGGCACTCCCCAATCGGGGCCTCCCCCAACTCCTGGGCCATCCCAAGATAACGACACCGACTGGGGGTATTGATGGACAAAACCCAGCCTGCTTCCACAAAAACATCCCAATGCCCTCACCCGTAGTCGACCCCTCGATTTGCGGCTCTATATGACCACACCCTCAAACAAACATCCCCCTCTTTCCTCCCTCCCCCTGCTGTACAACTCCGCACGCCCTAGATACCACAGGCACAATGCGGCTCACTAACAATCAAAACAGAGCCGAGGGAATTAGAAAAAAGTACGGGTAGAAGAGGGATATTCAGAGATCAGGGCAAGTCTCCCGAGTCTCTGCTCTCTCCTCTACCTGATAGACCAGGACAAACATGGCCACCTTTACAGATGCAGAGATCGACGAGCTATTTGAGACAAGTGGAACTGTCATTGACAACATAATTACAGCCCAGGGTAAACCAGCAGAGACTGTTGGAAGGAGTGCAATCCCACAAGGCAAGACCAAGGTGCTGAGCGCAGCATGGGAGAAGCATGGGAGCATCCAGCCACCGGCCAGTCAAGACAACCCCGATCGACAGGACAGATCTGACAAACAACCATCCACACCCGAGCAAACGACCCCGCATGACAGCCCGCCGGCCACATCCGCCGACCAGCCCCCCACCCAGGCCACAGACGAAGCCGTCGACACACAGTTCAGGACCGGAGCAAGCAACTCTCTGCTGTTGATGCTTGACAAGCTCAGCAATAAATCGTCCAATGCTAAAAAGGGCCCATGGTCGAGCCCCCAAGAGGGGAATCACCAACGTCCGACTCAACAGCAGGGGAGTCAACCCAGTCGCGGAAACAGTCAGGAAAGACCGCAGAACCAAGTCAAGGCCGCCCCTGGAAACCAGGGCACAGACGTGAACACAGCATATCATGGACAATGGGAGGAGTCACAACTATCAGCTGGTGCAACCCCTCATGCTCTCCGATCAAGGCAGAGCCAAGACAATACCCTTGTATCTGCGGATCATGTCCAGCCACCTGTAGACTTTGTGCAAGCGATGATGTCTATGATGGAGGCGATATCACAGAGAGTAAGTAAGGTTGACTATCAGCTAGATCTTGTCTTGAAACAGACATCCTCCATCCCTATGATGCGGTCCGAAATCCAACAGCTGAAAACATCTGTTGCAGTCATGGAAGCCAACTTGGGAATGATGAAGATTCTGGATCCCGGTTGTGCCAACATTTCATCTCTGAGTGATCTACGGGCAGTTGCCCGATCTCACCCGGTTTTAGTTTCAGGCCCTGGAGACCCCTCTCCCTATGTGACACAAGGAGGCGAAATGGCACTTAATAAACTTTCGCAACCAGTGCCACATCCATCTGAATTGATTAAACCCGCCACTGCATGCGGGCCTGATATAGGAGTGGAAAAGGACACTGTCCGTGCATTGATCATGTCACGCCCAATGCACCCGAGTTCTTCAGCCAAGCTCCTAAGCAAGTTAGATGCAGCCGGGTCGATCGAGGAAATCAGGAAAATCAAGCGCCTTGCTCTAAATGGCTAATTACTACTGCCACACGTAGCGGGTCCCTGTCCACTCGGCATCACACGGAATCTGCACCGAGTTCCCCCTCTAGATTAGAAAAAATACGGGTAGAACCGCCACCATGTTCGTGTTCCTGGTCCTGCTGCCACTGGTAAGCTCCCAATGTGTAAACTTAACCACAAGAACCCAGCTCCCACCTGCCTACACCAACAGCTTCACCAGAGGCGTTTATTACCCCGACAAGGTATTCCGGTCTTCTGTTCTGCACTCTACCCAGGACCTGTTTCTGCCCTTTTTCAGCAACGTGACATGGTTCCACGCCATCCACGTGTCTGGCACAAACGGCACCAAGCGGTTTGATAATCCTGTGCTCCCTTTCAATGACGGCGTGTACTTCGCCTCTACTGAGAAGAGCAACATCATCCGGGGCTGGATCTTTGGCACAACACTGGACTCTAAAACCCAGAGCCTGCTGATCGTGAACAACGCCACCAACGTGGTGATTAAGGTGTGCGAGTTCCAGTTCTGCAATGACCCTTTCCTCGGCGTGTACTACCACAAGAACAACAAAAGTTGGATGGAAAGCGAATTCAGGGTGTACTCAAGCGCCAACAACTGTACCTTCGAGTACGTGAGCCAGCCTTTCCTGATGGACCTAGAAGGTAAGCAGGGCAATTTCAAGAACCTCAGAGAGTTCGTGTTCAAGAATATTGACGGCTACTTCAAAATCTACAGCAAGCACACCCCAATCAACCTGGTGCGGGACCTGCCCCAGGGCTTTAGCGCGCTGGAGCCTCTGGTGGACCTGCCTATCGGCATCAACATCACCCGGTTCCAGACACTGCTGGCTCTGCATAGAAGCTACCTGACACCTGGCGACAGTTCTTCTGGCTGGACAGCCGGCGCCGCCGCCTACTACGTGGGCTACCTGCAGCCTAGAACATTCCTGCTGAAATACAACGAGAACGGCACGATCACAGACGCCGTGGACTGCGCCCTGGATCCCCTGTCTGAGACAAAGTGCACCCTGAAGTCTTTCACCGTGGAGAAGGGCATCTACCAGACCTCCAACTTCAGAGTGCAGCCTACCGAATCCATCGTGCGCTTTCCCAACATCACCAACCTGTGCCCCTTCGGCGAGGTCTTTAATGCCACGAGATTCGCCAGCGTGTATGCCTGGAACAGAAAGAGAATCAGCAACTGCGTGGCCGACTACAGCGTGCTGTACAACAGCGCCTCTTTCAGCACATTTAAGTGCTACGGAGTGTCTCCTACCAAACTCAACGATCTGTGCTTCACGAACGTGTATGCCGACAGCTTCGTGATCCGAGGAGATGAGGTGCGGCAGATCGCTCCAGGACAGACAGGCAAGATCGCCGACTACAACTACAAGCTGCCCGACGACTTTACCGGCTGCGTGATCGCTTGGAACAGCAATAACCTGGACTCAAAGGTTGGAGGAAACTACAACTACCTGTACAGACTGTTCAGAAAGTCCAACCTGAAGCCCTTCGAGAGAGACATCTCTACAGAAATCTACCAGGCCGGCAGCACCCCATGTAACGGCGTGGAAGGCTTCAACTGCTACTTCCCTCTGCAGTCTTATGGCTTCCAGCCCACAAACGGAGTGGGCTATCAGCCTTACCGCGTGGTTGTCCTGAGCTTTGAGCTGCTGCATGCCCCTGCTACGGTGTGTGGACCTAAGAAGTCCACCAACCTGGTGAAGAACAAGTGTGTGAACTTCAACTTCAACGGCCTGACCGGCACCGGGGTGCTGACAGAGTCTAACAAGAAATTCCTGCCATTCCAGCAATTCGGCCGGGACATCGCCGACACCACCGACGCCGTGCGGGATCCTCAGACCCTCGAAATCCTGGACATCACCCCCTGTAGCTTCGGCGGCGTGAGCGTGATCACCCCTGGCACAAACACCAGCAATCAAGTGGCTGTCCTGTACCAGGATGTCAATTGCACAGAAGTGCCTGTGGCCATCCACGCCGATCAGCTGACCCCCACCTGGCGGGTGTACTCGACAGGAAGCAACGTGTTTCAAACAAGAGCCGGCTGCCTGATCGGGGCCGAGCACGTGAACAATTCCTACGAGTGCGACATCCCCATCGGCGCCGGCATCTGTGCCTCTTACCAGACACAGACCAATTCCCCTCGTAGAGCCAGATCCGTGGCCAGCCAGAGCATCATCGCCTACACCATGAGCCTGGGCGCCGAAAACAGCGTTGCATATTCCAACAACAGCATCGCCATCCCTACCAACTTCACCATCAGCGTGACCACAGAAATCCTGCCTGTGTCCATGACCAAGACAAGCGTTGATTGCACCATGTACATCTGCGGCGATAGCACAGAGTGCAGCAATCTGCTGCTGCAGTACGGTAGCTTCTGCACCCAGCTGAATAGAGCCCTGACCGGCATCGCTGTGGAACAGGACAAAAACACCCAGGAGGTCTTCGCCCAGGTGAAGCAAATCTACAAGACCCCTCCAATCAAGGACTTCGGAGGCTTTAACTTTAGCCAGATCCTGCCTGATCCCTCCAAGCCTAGCAAACGGAGTcctATCGAGGACCTGCTCTTCAACAAGGTGACCCTGGCTGACGCCGGCTTCATTAAGCAGTACGGCGATTGCCTCGGCGACATCGCTGCAAGAGACCTGATCTGCGCCCAGAAGTTCAACGGCCTGACCGTGCTGCCTCCTCTCCTGACAGACGAGATGATCGCCCAGTACACCTCTGCCCTTCTGGCTGGCACCATCACCAGCGGATGGACCTTTGGAGCCGGAcctGCCCTGCAGATCCCTTTCcctATGCAGATGGCCTACAGATTCAACGGGATCGGAGTGACCCAAAACGTGCTGTATGAAAACCAGAAACTGATCGCCAATCAGTTTAACAGCGCCATCGGCAAAATCCAGGATAGCCTGTCCAGCACCccaAGCGCCCTCGGCAAGCTGCAAGATGTGGTGAATCAAAATGCCCAAGCCCTGAACACACTGGTGAAGCAGCTGAGCAGCAACTTCGGCGCCATCAGCAGCGTGCTGAACGACATCCTGAGCAGACTGGACccacctGAAGCCGAGGTGCAGATCGACAGACTGATCACAGGCAGACTGCAGTCCCTGCAGACCTACGTGACCCAGCAGTTGATTAGAGCCGCTGAGATTAGAGCCAGTGCCAACCTGGCTGCCACAAAGATGTCAGAATGCGTGCTGGGCCAGAGCAAGAGAGTGGACTTCTGCGGCAAAGGCTACCACCTGATGAGCTTTCCTCAGTCTGCACCCCACGGCGTGGTGTTTCTCCACGTGACATACGTGCCCGCGCAAGAAAAGAACTTTACAACCGCCCCAGCGATCTGCCACGACGGCAAGGCCCACTTCCCTCGGGAGGGTGTGTTCGTGAGCAATGGAACACACTGGTTCGTCACCCAGCGGAACTTCTACGAGCCTCAGATCATTACCACCGACAACACCTTCGTGAGCGGCAACTGTGACGTCGTTATCGGCATCGTGAACAATACCGTGTACGACCCCCTGCAGCCTGAGCTGGATAGCTTCAAAGAGGAACTGGACAAGTACTTCAAGAACCACACAAGCCCCGACGTGGACCTAGGCGACATCTCTGGAATCAACGCCAGCGTGGTGAACATCCAAAAGGAAATCGACAGACTGAACGAGGTGGCCAAGAATCTGAATGAAAGCCTGATCGATCTGCAGGAGCTGGGCAAGTACGAGCAGTACATCAAATGGCCTTGGTACATCTGGCTGGGCTTCATCGCTGGTCTGATCGCTATCGTGATGGTGACCATTATGCTGTGCTGCATGACCTCCTGCTGCTCTTGCCTGAAGGGCTGTTGTTCTTGCGGCTCTTGCTGCAAGTTCGACGAGGATGACTCTGAACCTGTTCTGAAGGGCgtgaagctgcactacacctgataaacgcgtACCCAAGGTCCAACTCTCCAAGCGGCAATCCTCTCTCGCTTCCTCAGCCCCACTGAATGGTCGCGTAACCGTAATTAATCTAGCTACATTTAAGATTAAGAAAAAATACGGGTAGAATTGGAGTGCCCCAATTGTGCCAAGATGGACTCATCTAGGACAATTGGGCTGTACTTTGATTCTGCCCATTCTTCTAGCAACCTGTTAGCATTTCCGATCGTCCTACAAGGCACAGGAGATGGGAAGAAGCAAATCGCCCCGCAATATAGGATCCAGCGCCTTGACTTGTGGACTGATAGTAAGGAGGACTCAGTATTCATCACCACCTATGGATTCATCTTTCAAGTTGGGAATGAAGAAGCCACTGTCGGCATGATCGATGATAAACCCAAGCGCGAGTTACTTTCCGCTGCGATGCTCTGCCTAGGAAGCGTCCCAAATACCGGAGACCTTATTGAGCTGGCAAGGGCCTGTCTCACTATGATAGTCACATGCAAGAAGAGTGCAACTAATACTGAGAGAATGGTTTTCTCAGTAGTGCAGGCACCCCAAGTGCTGCAAAGCTGTAGGGTTGTGGCAAACAAATACTCATCAGTGAATGCAGTCAAGCACGTGAAAGCGCCAGAGAAGATTCCCGGGAGTGGAACCCTAGAATACAAGGTGAACTTTGTCTCCTTGACTGTGGTACCGAAGAAGGATGTCTACAAGATCCCAGCTGCAGTATTGAAGGTTTCTGGCTCGAGTCTGTACAATCTTGCGCTCAATGTCACTATTAATGTGGAGGTAGACCCGAGGAGTCCTTTGGTTAAATCTTTGTCTAAGTCTGACAGCGGATACTATGCTAACCTCTTCTTGCATATTGGACTTATGACCACCGTAGATAGGAAGGGGAAGAAAGTGACATTTGACAAGCTGGAAAAGAAAATAAGGAGCCTTGATCTATCTGTCGGGCTCAGTGATGTGCTCGGGCCTTCCGTGTTGGTAAAAGCAAGAGGTGCACGGACTAAGCTTTTGGCACCTTTCTTCTCTAGCAGTGGGACAGCCTGCTATCCCATAGCAAATGCTTCTCCTCAGGTGGCCAAGATACTCTGGAGTCAAACCGCGTGCCTGCGGAGCGTTAAAATCATTATCCAAGCAGGTACCCAACGCGCTGTCGCAGTGACCGCCGACCACGAGGTTACCTCTACTAAGCTGGAGAAGGGGCACACCCTTGCCAAATACAATCCTTTTAAGAAATAAGCTGCGTCTCTGAGATTGCGCTCCGCCCACTCACCCAGATCATCATGACACAAAAAACTAATCTGTCTTGATTATTTACAGTTAGTTTACCTGTCTATCAAGTTAGAAAAAACACGGGTAGAAGATTCTGGATCCCGGTTGGCGCCCTCCAGGTGCAAGttaattaaATGGGCTCCAGACCTTCTACCAAGAACCCAGCACCTATGATGCTGACTATCCGGGTTGCGCTGGTACTGAGTTGCATCTGTCCGGCAAACTCCATTGATGGCAGGCCTCTTGCAGCTGCAGGAATTGTGGTTACAGGAGACAAAGCCGTCAACATATACACCTCATCCCAGACAGGATCAATCATAGTTAAGCTCCTCCCGAATCTGCCCAAGGATAAGGAGGCATGTGCGAAAGCCCCCTTGGATGCATACAACAGGACATTGACCACTTTGCTCACCCCCCTTGGTGACTCTATCCGTAGGATACAAGAGTCTGTGACTACATCTGGAGGGGGGAGACAGGGGCGCCTTATAGGCGCCATTATTGGCGGTGTGGCTCTTGGGGTTGCAACTGCCGCACAAATAACAGCGGCCGCAGCTCTGATACAAGCCAAACAAAATGCTGCCAACATCCTCCGACTTAAAGAGAGCATTGCCGCAACCAATGAGGCTGTGCATGAGGTCACTGACGGATTATCGCAACTAGCAGTGGCAGTTGGGAAGATGCAGCAGTTTGTTAATGACCAATTTAATAAAACAGCTCAGGAATTAGACTGCATCAAAATTGCACAGCAAGTTGGTGTAGAGCTCAACCTGTACCTAACCGAATTGACTACAGTATTCGGACCACAAATCACTTCACCTGCTTTAAACAAGCTGACTATTCAGGCACTTTACAATCTAGCTGGTGGAAATATGGATTACTTATTGACTAAGTTAGGTGTAGGGAACAATCAACTCAGCTCATTAATCGGTAGCGGCTTAATCACtGGcAACCCTATTCTATACGACTCACAGACTCAACTCTTGGGTATACAGGTAACTgcaCCTTCAGTCGGGAACCTAAATAATATGCGTGCCACCTACTTGGAAACCTTATCCGTAAGCACAACCAGGGGATTTGCCTCGGCACTTGTCCCCAAAGTGGTGACACAGGTCGGTTCTGTGATAGAAGAACTTGACACCTCATACTGTATAGAAACTGACTTAGATTTATATTGTACAAGAATAGTAACGTTCCCTATGTCCCCTGGTATTTATTCCTGCTTGAGCGGCAATACGTCGGCCTGTATGTACTCAAAGACCGAAGGCGCACTTACTACACCATACATGACTATCAAAGGTTCAGTCATCGCCAACTGCAAGATGACAACATGTAGATGTGTAAACCCCCCGGGTATCATATCGCAAAACTATGGAGAAGCCGTGTCTCTAATAGATAAACAATCATGCAATGTTTTATCCTTAGGCGGGATAACTTTAAGGCTCAGTGGGGAATTCGATGTAACTTATCAGAAGAATATCTCAATACAAGATTGTCAAGTAATAATAACAGGCAATCTTGATATCTCAACTGAGGTTGGGAATGTCAACAACTCGATCAGTAATGCTTTGAATAAGTTAGAGGAAAGCAACAGAAAACTAGACAAAGTCAATGTCAAACTGACTAGCACATCTGCTCTCATTACgTATATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTGATTCTAGCATGCTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTTATTATGGCTTGGGAATAATACaCTcGATCAGATGAGAGCCACTACAAAAATGTGAACACAGATGAGGAACGAAGGTTTCCCTAATAGTAATTTGTGTGAAAGTTCTGGTAGTCTGTCAGTTCAGAGAGTTAAGAAAAAACTACCGGTTGTAGATGACCAAAGGACGATATACGGGTAGAACGGTAAGAGAGGCCGCCCCTCAATTGCGAGCCAGGCTTCACAACCTCCGTTCTACCGCTTCACCGACAACAGTCCTCAATCATGGACCGCGCCGTTAGCCAAGTTGCGTTAGAGAATGATGAAAGAGAGGCAAAAAATACATGGCGCTTGATATTCCGGATTGCAATCTTATTCTTAACAGTAGTGACCTTGGCTATATCTGTAGCCTCCCTTTTATATAGCATGGGGGCTAGCACACCTAGCGATCTTGTAGGCATACCGACTAGGATTTCCAGGGCAGAAGAAAAGATTACATCTACACTTGGTTCCAATCAAGATGTAGTAGATAGGATATATAAGCAAGTGGCCCTTGAGTCTCCGTTGGCATTGTTAAATACTGAGACCACAATTATGAACGCAATAACATCTCTCTCTTATCAGATTAATGGAGCTGCAAACAACAGTGGGTGGGGGGCACCTATCCATGACCCAGATTATATAGGGGGGATAGGCAAAGAACTCATTGTAGATGATGCTAGTGATGTCACATCATTCTATCCCTCTGCATTTCAAGAACATCTGAATTTTATCCCGGCGCCTACTACAGGATCAGGTTGCACTCGAATACCCTCATTTGACATGAGTGCTACCCATTACTGCTACACCCATAATGTAATATTGTCTGGATGCAGAGATCACTCACATTCATATCAGTATTTAGCACTTGGTGTGCTCCGGACATCTGCAACAGGGAGGGTATTCTTTTCTACTCTGCGTTCCATCAACCTGGACGACACCCAAAATCGGAAGTCTTGCAGTGTGAGTGCAACTCCCCTGGGTTGTGATATGCTGTGCTCGAAAGTCACGGAGACAGAGGAAGAAGATTATAACTCAGCTGTCCCTACGCGGATGGTACATGGGAGGTTAGGGTTCGACGGCCAGTACCACGAAAAGGACCTAGATGTCACAACATTATTCGGGGACTGGGTGGCCAACTACCCAGGAGTAGGGGGTGGATCTTTTATTGACAGCCGCGTATGGTTCTCAGTCTACGGAGGGTTAAAACCCAATTCACCCAGTGACACTGTACAGGAAGGGAAATATGTGATATACAAGCGATACAATGACACATGCCCAGATGAGCAAGACTACCAGATTCGAATGGCCAAGTCTTCGTATAAGCCTGGACGGTTTGGTGGGAAACGCATACAGCAGGCTATCTTATCTATCAAGGTGTCAACATCCTTAGGCGAAGACCCGGTACTGACTGTACCGCCCAACACAGTCACACTCATGGGGGCCGAAGGCAGAATTCTCACAGTAGGGACATCTCATTTCTTGTATCAACGAGGGTCATCATACTTCTCTCCCGCGTTATTATATCCTATGACAGTCAGCAACAAAACAGCCACTCTTCATAGTCCTTATACATTCAATGCCTTCACTCGGCCAGGTAGTATCCCTTGCCAGGCTTCAGCAAGATGCCCCAACTCGTGTGTTACTGGAGTCTATACAGATCCATATCCCCTAATCTTCTATAGAAACCACACCTTGCGAGGGGTATTCGGGACAATGCTTGATGGTGTACAAGCAAGACTTAACCCTGCGTCTGCAGTATTCGATAGCACATCCCGCAGTCGCATTACTCGAGTGAGTTCAAGCAGTACCAAAGCAGCATACACAACATCAACTTGTTTTAAAGTGGTCAAGACTAATAAGACCTATTGTCTCAGCATTGCTGAAATATCTAATACTCTCTTCGGAGAATTCAGAATCGTCCCGTTACTAGTTGAGATCCTCAAAGATGACGGGGTTAGAGAAGCCAGGTCTGGCTAGggcgcgccTTGAGTCAATTATAAAGGAGTTGGAAAGATGGCATTGTATCACCTATCTTCTGCGACATCAAGAATCAAACCGAATGCCGGCGCGTGCTCGAATTCCATGTTGCCAGTTGACCACAATCAGCCAGTGCTCATGCGATCAGATTAAGCCTTGTCATTAATCTCTTGATTAAGAAAAAATGTAAGTGGCAATGAGATACAAGGCAAAACAGCTCATGGTAAATAATACGGGTAGGACATGGCGAGCTCCGGTCCTGAAAGGGCAGAGCATCAGATTATCCTACCAGAGCCACACCTGTCTTCACCATTGGTCAAGCACAAACTACTCTATTACTGGAAATTAACTGGGCTACCGCTTCCTGATGAATGTGACTTCGACCACCTCATTCTCAGCCGACAATGGAAAAAAATACTTGAATCGGCCTCTCCTGATACTGAGAGAATGATAAAACTCGGAAGGGCAGTACACCAAACTCTTAACCACAATTCCAGAATAACCGGAGTGCTCCACCCCAGGTGTTTAGAACAACTGGCTAATATTGAGGTCCCAGATTCAACCAACAAATTTCGGAAGATTGAGAAGAAGATCCAAATTCACAACACGAGATATGGAGAACTGTTCACAAGGCTGTGTACGCATATAGAGAAGAAACTGCTGGGGTCATCTTGGTCTAACAATGTCCCCCGGTCAGAGGAGTTCAGCAGCATTCGTACGGATCCGGCATTCTGGTTTCACTCAAAATGGTCCACAGCCAAGTTTGCATGGCTCCATATAAAACAGATCCAGAGGCATCTGATGGTGGCAGCTAAGACAAGGTCTGCGGCCAACAAATTGGTGATGCTAACCCATAAGGTAGGCCAAGTCTTTGTCACTCCTGAACTTGTCGTTGTGACGCATACGAATGAGAACAAGTTCACATGTCTTACCCAGGAACTTGTATTGATGTATGCAGATATGATGGAGGGCAGAGATATGGTCAACATAATATCAACCACGGCGGTGCATCTCAGAAGCTTATCAGAGAAAATTGATGACATTTTGCGGTTAATAGACGCTCTGGCAAAAGACTTGGGTAATCAAGTCTACGATGTTGTATCACTAATGGAGGGATTTGCATACGGAGCTGTCCAGCTACTCGAGCCGTCAGGTACATTTGCAGGAGATTTCTTCGCATTCAACCTGCAGGAGCTTAAAGACATTCTAATTGGCCTCCTCCCCAATGATATAGCAGAATCCGTGACTCATGCAATCGCTACTGTATTCTCTGGTTTAGAACAGAATCAAGCAGCTGAGATGTTGTGTCTGTTGCGTCTGTGGGGTCACCCACTGCTTGAGTCCCGTATTGCAGCAAAGGCAGTCAGGAGCCAAATGTGCGCACCGAAAATGGTAGACTTTGATATGATCCTTCAGGTACTGTCTTTCTTCAAGGGAACAATCATCAACGGGTACAGAAAGAAGAATGCAGGTGTGTGGCCGCGAGTCAAAGTGGATACAATATATGGGAAGGTCATTGGGCAACTACATGCAGATTCAGCAGAGATTTCACACGATATCATGTTGAGAGAGTATAAGAGTTTATCTGCACTTGAATTTGAGCCATGTATAGAATATGACCCTGTCACCAACCTGAGCATGTTCCTAAAAGACAAGGCAATCGCACACCCCAACGATAATTGGCTTGCCTCGTTTAGGCGGAACCTTCTCTCCGAAGACCAGAAGAAACATGTAAAAGAAGCAACTTCGACTAATCGCCTCTTGATAGAGTTTTTAGAGTCAAATGATTTTGATCCATATAAAGAGATGGAATATCTGACGACCCTTGAGTACCTTAGAGATGACAATGTGGCAGTATCATACTCGCTCAAGGAGAAGGAAGTGAAAGTTAATGGACGGATCTTCGCTAAGCTGACAAAGAAGTTAAGGAACTGTCAGGTGATGGCGGAAGGGATCCTAGCCGATCAGATTGCACCTTTCTTTCAGGGAAATGGAGTCATTCAGGATAGCATATCCTTGACCAAGAGTATGCTAGCGATGAGTCAACTGTCTTTTAACAGCAATAAGAAACGTATCACTGACTGTAAAGAAAGAGTATCTTCAAACCGCAATCATGATCCGAAAAGCAAGAACCGTCGGAGAGTTGCAACCTTCATAACAACTGACCTGCAAAAGTACTGTCTTAATTGGAGATATCAGACAATCAAATTGTTCGCTCATGCCATCAATCAGTTGATGGGCCTACCTCACTTCTTCGAATGGATTCACCTAAGACTGATGGACACTACGATGTTCGTAGGAGACCCTTTCAATCCTCCAAGTGACCCTACTGACTGTGACCTCTCAAGAGTCCCTAATGATGACATATATATTGTCAGTGCCAGAGGGGGTATCGAAGGATTATGCCAGAAGCTATGGACAATGATCTCAATTGCTGCAATCCAACTTGCTGCAGCTAGATCGCATTGTCGTGTTGCCTGTATGGTACAGGGTGATAATCAAGTAATAGCAGTAACGAGAGAGGTAAGATCAGACGACTCTCCGGAGATGGTGTTGACACAGTTGCATCAAGCCAGTGATAATTTCTTCAAGGAATTAATTCATGTCAATCATTTGATTGGCCATAATTTGAAGGATCGTGAAACCATCAGGTCAGACACATTCTTCATATACAGCAAACGAATCTTCAAAGATGGAGCAATCCTCAGTCAAGTCCTCAAAAATTCATCTAAATTAGTGCTAGTGTCAGGTGATCTCAGTGAAAACACCGTAATGTCCTGTGCCAACATTGCCTCTACTGTAGCACGGCTATGCGAGAACGGGCTTCCCAAAGACTTCTGTTACTATTTAAACTATATAATGAGTTGTGTGCAGACATACTTTGACTCTGAGTTCTCCATCACCAACAATTCGCACCCCGATCTTAATCAGTCGTGGATTGAGGACATCTCTTTTGTGCACTCATATGTTCTGACTCCTGCCCAATTAGGGGGACTGAGTAACCTTCAATACTCAAGGCTCTACACTAGAAATATCGGTGACCCGGGGACTACTGCTTTTGCAGAGATCAAGCGACTAGAAGCAGTGGGATTACTGAGTCCTAACATTATGACTAATATCTTAACTAGGCCGCCTGGGAATGGAGATTGGGCCAGTCTGTGCAACGACCCATACTCTTTCAATTTTGAGACTGTTGCAAGCCCAAATATTGTTCTTAAGAAACATACGCAAAGAGTCCTATTTGAAACTTGTTCAAATCCCTTATTGTCTGGAGTGCACACAGAGGATAATGAGGCAGAAGAGAAGGCATTGGCTGAATTCTTGCTTAATCAAGAGGTGATTCATCCCCGCGTTGCGCATGCCATCATGGAGGCAAGCTCTGTAGGTAGGAGAAAGCAAATTCAAGGGCTTGTTGACACAACAAACACCGTAATTAAGATTGCGCTTACTAGGAGGCCATTAGGCATCAAGAGGCTGATGCGGATAGTCAATTATTCTAGCATGCATGCAATGCTGTTTAGAGACGATGTTTTTTCCTCCAGTAGATCCAACCACCCCTTAGTCTCTTCTAATATGTGTTCTCTGACACTGGCAGACTATGCACGGAATAGAAGCTGGTCACCTTTGACGGGAGGCAGGAAAATACTGGGTGTATCTAATCCTGATACGATAGAACTCGTAGAGGGTGAGATTCTTAGTGTAAGCGGAGGGTGTACAAGATGTGACAGCGGAGATGAACAATTTACTTGGTTCCATCTTCCAAGCAATATAGAATTGACCGATGACACCAGCAAGAATCCTCCGATGAGGGTACCATATCTCGGGTCAAAGACACAGGAGAGGAGAGCTGCCTCACTTGCAAAAATAGCTCATATGTCGCCACATGTAAAGGCTGCCCTAAGGGCATCATCCGTGTTGATCTGGGCTTATGGGGATAATGAAGTAAATTGGACTGCTGCTCTTACGATTGCAAAATCTCGGTGTAATGTAAACTTAGAGTATCTTCGGTTACTGTCCCCTTTACCCACGGCTGGGAATCTTCAACATAGACTAGATGATGGTATAACTCAGATGACATTCACCCCTGCATCTCTCTACAGGgtgtcaccttacattcacatatccaatgattctcaaaggctgttcactgaagaaggagtcaaagaggggaatgtggtttaccaacagatcATGCTCTTGGGTTTATCTCTAATCGAATCGATCTTTCCAATGACAACAACCAGGACATATGATGAGATCACACTGCACCTAGATAGTAAATTTAGTTGCTGTATCAGAGAAGCACCTGTTGCGGTTCCTTTCGAGCTACTTGGGGTGGTACCGGAACTGAGGACAGTGACCTCAAATAAGTTTATGTATGATCCTAGCCCTGTATCGGAGGGAGACTTTGCGAGACTTGACTTAGCTATCTTCAAGAGTTATGAGCTTAATCTGGAGTCATATCCCACGATAGAGCTAATGAACATTCTTTCAATATCCAGCGGGAAGTTGATTGGCCAGTCTGTGGTTTCTTATGATGAAGATACCTCCATAAAGAATGACGCCATAATAGTGTATGACAATACCCGAAATTGGATCAGTGAAGCTCAGAATTCAGATGTGGTCCGCCTATTTGAATATGCAGCACTTGAAGTGCTCCTCGACTGTTCTTACCAACTCTATTACCTGAGAGTAAGAGGCCTAGACAATATTGTCTTATATATGGGTGATTTATACAAGAATATGCCAGGAATTCTACTTTCCAACATTGCAGCTACAATATCTCATCCCGTCATTCATTCAAGGTTACATGCAGTGGGCCTGGTCAACCATGACGGATCACACCAACTTGCAGATACGGATTTTATCGAAATGTCTGCAAAACTATTAGTATCTTGCACCCGACGTGTGATCTCCGGCTTATATTCAGGAAATAAGTATGATCTGCTGTTCCCATCTGTCTTAGATGATAACCTGAATGAGAAGATGCTTCAGCTGATATCCCGGTTATGCTGTCTGTACACGGTACTCTTTGCTACAACAAGAGAAATCCCGAAAATAAGAGGCTTAACTGCAGAAGAGAAATGTTCAATACTCACTGAGTATTTACTGTCGGATGCTGTGAAACCATTACTTAGCCCCGATCAAGTGAGCTCTATCATGTCTCCTAACATAATTACATTCCCAGCTAATCTGTACTACATGTCTCGGAAGAGCCTCAATTTGATCAGGGAAAGGGAGGACAGGGATACTATCCTGGCGTTGTTGTTCCCCCAAGAGCCATTATTAGAGTTCCCTTCTGTGCAAGATATTGGTGCTCGAGTGAAAGATCCATTCACCCGACAACCTGCGGCATTTTTGCAAGAGTTAGATTTGAGTGCTCCAGCAAGGTATGACGCATTCACACTTAGTCAGATTCATCCTGAACTCACATCTCCAAATCCGGAGGAAGACTACTTAGTACGATACTTGTTCAGAGGGATAGGGACTGCATCTTCCTCTTGGTATAAGGCATCTCATCTCCTTTCTGTACCCGAGGTAAGATGTGCAAGACACGGGAACTCCTTATACTTAGCTGAAGGGAGCGGAGCCATCATGAGTCTTCTCGAACTGCATGTACCACATGAAACTATCTATTACAATACGCTCTTTTCAAATGAGATGAACCCCCCGCAACGACATTTCGGGCCGACCCCAACTCAGTTTTTGAATTCGGTTGTTTATAGGAATCTACAGGCGGAGGTAACATGCAAAGATGGATTTGTCCAAGAGTTCCGTCCATTATGGAGAGAAAATACAGAGGAAAGTGACCTGACCTCAGATAAAGCAGTGGGGTATATTACATCTGCAGTGCCCTACAGATCTGTATCATTGCTGCATTGTGACATTGAAATTCCTCCAGGGTCCAATCAAAGCTTACTAGATCAACTAGCTATCAATTTATCTCTGATTGCCATGCATTCTGTAAGGGAGGGCGGGGTAGTAATCATCAAAGTGTTGTATGCAATGGGATACTACTTTCATCTACTCATGAACTTGTTTGCTCCGTGTTCCACAAAAGGATATATTCTCTCTAATGGTTATGCATGTCGAGGAGATATGGAGTGTTACCTGGTATTTGTCATGGGTTACCTGGGCGGGCCTACATTTGTACATGAGGTGGTGAGGATGGCAAAAACTCTGGTGCAGCGGCACGGTACGCTCTTGTCTAAATCAGATGAGATCACACTGACCAGGTTATTCACCTCACAGCGGCAGCGTGTGACAGACATCCTATCCAGTCCTTTACCAAGATTAATAAAGTACTTGAGGAAGAATATTGACACTGCGCTGATTGAAGCCGGGGGACAGCCCGTCCGTCCATTCTGTGCGGAGAGTCTGGTGAGCACGCTAGCGAACATAACTCAGATAACCCAGATTATCGCTAGTCACATTGACACAGTTATCCGGTCTGTGATATATATGGAAGCTGAGGGTGATCTCGCTGACACAGTATTTCTATTTACCCCTTACAATCTCTCTACTGACGGGAAAAAGAGGACATCACTTATACAGTGCACGAGACAGATCCTAGAGGTTACAATACTAGGTCTTAGAGTCGAAAATCTCAATAAAATAGGCGATATAATCAGCCTAGTGCTTAAAGGCATGATCTCCATGGAGGACCTTATCCCACTAAGGACATACTTGAAGCATAGTACCTGCCCTAAATATTTGAAGGCTGTCCTAGGTATTACCAAACTCAAAGAAATGTTTACAGACACTTCTGTATTGTACTTGACTCGTGCTCAACAAAAATTCTACATGAAAACTATAGGCAATGCAGTCAAAGGATATTACAGTAACTGTGACTCTTAACGAAAATCACATATTAATAGGCTCCTTTTTTGGCCAATTGTATTCTTGTTGATTTAATCATATTATGTTAGAAAAAAGTTGAACCCTGACTCCTTAGGACTCGAATTCGAACTCAAATAAATGTCTTAAAAAAAGGTTGCGCACAATTATTCTTGAGTGTAGTCTCGTCATTCACCAAATCTTTGTTTGGTGGCCGGCATGGTCCCAGCCTCCTCGCTGGCGCCGGCTGGGCAACATTCCGAGGGGACCGTCCCCTCGGTAATGGCGAATGGGACGTCGACTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTATAT SEQ ID NO:VSPYIHISNDSQRLFTEEGVKEGNVVYQQI 20; amino acid sequence for stabilizingsegment in L protein SEQ ID NO:GCACCGAGTTCCCCCTCTAGATTAGAAAAAATACGGGTAGAACCGCCAC 21; forward primer forexpressing spike protein SEQ ID NO:GTTGGACCTTGGGTACGCGTTTATCAGGTGTAGTGCAGCTTCAC 22; reverse primer forexpressing spike protein SEQ ID NO:TAATACGACTCACTATAGGGACCAAACAGAGAATCCGTGAGTTACGATAAAAGGCGAAGG 23; NDV-AGCAATTGAAGTCGCACGGGTAGAAGGTGTGAATCTCGAGTGCGAGCCCGAAGCACAAAC GFP-F3 aaTCGAGAAAGCCTTCTGCCAACATGTCTTCCGTATTTGATGAGTACGAACAGCTCCTCGCG MolecularGCTCAGACTCGCCCCAATGGAGCTCATGGAGGGGGAGAAAAAGGGAGTACCTTAAAAGTA CloneGACGTCCCGGTATTCACTCTTAACAGTGATGACCCAGAAGATAGATGGAGCTTTGTGGTA AF077761.1_TTCTGCCTCCGGATTGCTGTTAGCGAAGATGCCAACAAACCACTCAGGCAAGGTGCTCTC LaSota_KanATATCTCTTTTATGCTCCCACTCACAGGTAATGAGGAACCATGTTGCCATTGCAGGGAAA R (withCAGAATGAAGCCACATTGGCCGTGCTTGAGATTGATGGCTTTGCCAACGGCACGCCCCAG stabilizingTTCAACAATAGGAGTGGAGTGTCTGAAGAGAGAGCACAGAGATTTGCGATGATAGCAGGA sequence inTCTCTCCCTCGGGCATGCAGCAACGGAACCCCGTTCGTCACAGCCGGGGCAGAAGATGAT L)GCACCAGAAGACATCACCGATACCCTGGAGAGGATCCTCTCTATCCAGGCTCAAGTATGG (mesogenic)GTCACAGTAGCAAAAGCCATGACTGCGTATGAGACTGCAGATGAGTCGGAAACAAGGCGAATCAATAAGTATATGCAGCAAGGCAGGGTCCAAAAGAAATACATCCTCTACCCCGTATGCAGGAGCACAATCCAACTCACGATCAGACAGTCTCTTGCAGTCCGCATCTTTTTGGTTAGCGAGCTCAAGAGAGGCCGCAACACGGCAGGTGGTACCTCTACTTATTATAACCTGGTAGGGGACGTAGACTCATACATCAGGAATACCGGGCTTACTGCATTCTTCTTGACACTCAAGTACGGAATCAACACCAAGACATCAGCCCTTGCACTTAGTAGCCTCTCAGGCGACATCCAGAAGATGAAGCAGCTCATGCGTTTGTATCGGATGAAAGGAGATAATGCGCCGTACATGACATTACTTGGTGATAGTGACCAGATGAGCTTTGCGCCTGCCGAGTATGCACAACTTTACTCCTTTGCCATGGGTATGGCATCAGTCCTAGATAAAGGTACTGGGAAATACCAATTTGCCAGGGACTTTATGAGCACATCATTCTGGAGACTTGGAGTAGAGTACGCTCAGGCTCAGGGAAGTAGCATTAACGAGGATATGGCTGCCGAGCTAAAGCTAACCCCAGCAGCAATGAAGGGCCTGGCAGCTGCTGCCCAACGGGTCTCCGACGATACCAGCAGCATATACATGCCTACTCAACAAGTCGGAGTCCTCACTGGGCTTAGCGAGGGGGGGTCCCAAGCTCTACAAGGCGGATCGAATAGATCGCAAGGGCAACCAGAAGCCGGGGATGGGGAGACCCAATTCCTGGATCTGATGAGAGCGGTAGCAAATAGCATGAGGGAGGCGCCAAACTCTGCACAGGGCACTCCCCAATCGGGGCCTCCCCCAACTCCTGGGCCATCCCAAGATAACGACACCGACTGGGGGTATTGATGGACAAAACCCAGCCTGCTTCCACAAAAACATCCCAATGCCCTCACCCGTAGTCGACCCCTCGATTTGCGGCTCTATATGACCACACCCTCAAACAAACATCCCCCTCTTTCCTCCCTCCCCCTGCTGTACAACTCCGCACGCCCTAGATACCACAGGCACAATGCGGCTCACTAACAATCAAAACAGAGCCGAGGGAATTAGAAAAAAGTACGGGTAGAAGAGGGATATTCAGAGATCAGGGCAAGTCTCCCGAGTCTCTGCTCTCTCCTCTACCTGATAGACCAGGACAAACATGGCCACCTTTACAGATGCAGAGATCGACGAGCTATTTGAGACAAGTGGAACTGTCATTGACAACATAATTACAGCCCAGGGTAAACCAGCAGAGACTGTTGGAAGGAGTGCAATCCCACAAGGCAAGACCAAGGTGCTGAGCGCAGCATGGGAGAAGCATGGGAGCATCCAGCCACCGGCCAGTCAAGACAACCCCGATCGACAGGACAGATCTGACAAACAACCATCCACACCCGAGCAAACGACCCCGCATGACAGCCCGCCGGCCACATCCGCCGACCAGCCCCCCACCCAGGCCACAGACGAAGCCGTCGACACACAGTTCAGGACCGGAGCAAGCAACTCTCTGCTGTTGATGCTTGACAAGCTCAGCAATAAATCGTCCAATGCTAAAAAGGGCCCATGGTCGAGCCCCCAAGAGGGGAATCACCAACGTCCGACTCAACAGCAGGGGAGTCAACCCAGTCGCGGAAACAGTCAGGAAAGACCGCAGAACCAAGTCAAGGCCGCCCCTGGAAACCAGGGCACAGACGTGAACACAGCATATCATGGACAATGGGAGGAGTCACAACTATCAGCTGGTGCAACCCCTCATGCTCTCCGATCAAGGCAGAGCCAAGACAATACCCTTGTATCTGCGGATCATGTCCAGCCACCTGTAGACTTTGTGCAAGCGATGATGTCTATGATGGAGGCGATATCACAGAGAGTAAGTAAGGTTGACTATCAGCTAGATCTTGTCTTGAAACAGACATCCTCCATCCCTATGATGCGGTCCGAAATCCAACAGCTGAAAACATCTGTTGCAGTCATGGAAGCCAACTTGGGAATGATGAAGATTCTGGATCCCGGTTGTGCCAACATTTCATCTCTGAGTGATCTACGGGCAGTTGCCCGATCTCACCCGGTTTTAGTTTCAGGCCCTGGAGACCCCTCTCCCTATGTGACACAAGGAGGCGAAATGGCACTTAATAAACTTTCGCAACCAGTGCCACATCCATCTGAATTGATTAAACCCGCCACTGCATGCGGGCCTGATATAGGAGTGGAAAAGGACACTGTCCGTGCATTGATCATGTCACGCCCAATGCACCCGAGTTCTTCAGCCAAGCTCCTAAGCAAGTTAGATGCAGCCGGGTCGATCGAGGAAATCAGGAAAATCAAGCGCCTTGCTCTAAATGGCTAATTACTACTGCCACACGTAGCGGGTCCCTGTCCACTCGGCATCACACGGAATCTGCACCGAGTTCCCCCtctagaTTAGAAAAAATACGGGTAGAACCGCCACCATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCGCCCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAGTaATaaacgcgtACCCAAGGTCCAACTCTCCAAGCGGCAATCCTCTCTCGCTTCCTCAGCCCCACTGAATGGTCGCGTAACCGTAATTAATCTAGCTACATTTAAGATTAAGAAAAAATACGGGTAGAATTGGAGTGCCCCAATTGTGCCAAGATGGACTCATCTAGGACAATTGGGCTGTACTTTGATTCTGCCCATTCTTCTAGCAACCTGTTAGCATTTCCGATCGTCCTACAAGGCACAGGAGATGGGAAGAAGCAAATCGCCCCGCAATATAGGATCCAGCGCCTTGACTTGTGGACTGATAGTAAGGAGGACTCAGTATTCATCACCACCTATGGATTCATCTTTCAAGTTGGGAATGAAGAAGCCACTGTCGGCATGATCGATGATAAACCCAAGCGCGAGTTACTTTCCGCTGCGATGCTCTGCCTAGGAAGCGTCCCAAATACCGGAGACCTTATTGAGCTGGCAAGGGCCTGTCTCACTATGATAGTCACATGCAAGAAGAGTGCAACTAATACTGAGAGAATGGTTTTCTCAGTAGTGCAGGCACCCCAAGTGCTGCAAAGCTGTAGGGTTGTGGCAAACAAATACTCATCAGTGAATGCAGTCAAGCACGTGAAAGCGCCAGAGAAGATTCCCGGGAGTGGAACCCTAGAATACAAGGTGAACTTTGTCTCCTTGACTGTGGTACCGAAGAAGGATGTCTACAAGATCCCAGCTGCAGTATTGAAGGTTTCTGGCTCGAGTCTGTACAATCTTGCGCTCAATGTCACTATTAATGTGGAGGTAGACCCGAGGAGTCCTTTGGTTAAATCTTTGTCTAAGTCTGACAGCGGATACTATGCTAACCTCTTCTTGCATATTGGACTTATGACCACCGTAGATAGGAAGGGGAAGAAAGTGACATTTGACAAGCTGGAAAAGAAAATAAGGAGCCTTGATCTATCTGTCGGGCTCAGTGATGTGCTCGGGCCTTCCGTGTTGGTAAAAGCAAGAGGTGCACGGACTAAGCTTTTGGCACCTTTCTTCTCTAGCAGTGGGACAGCCTGCTATCCCATAGCAAATGCTTCTCCTCAGGTGGCCAAGATACTCTGGAGTCAAACCGCGTGCCTGCGGAGCGTTAAAATCATTATCCAAGCAGGTACCCAACGCGCTGTCGCAGTGACCGCCGACCACGAGGTTACCTCTACTAAGCTGGAGAAGGGGCACACCCTTGCCAAATACAATCCTTTTAAGAAATAAGCTGCGTCTCTGAGATTGCGCTCCGCCCACTCACCCAGATCATCATGACACAAAAAACTAATCTGTCTTGATTATTTACAGTTAGTTTACCTGTCTATCAAGTTAGAAAAAACACGGGTAGAAGATTCTGGATCCCGGTTGGCGCCCTCCAGGTGCAAGttaattaaATGGGCTCCAGACCTTCTACCAAGAACCCAGCACCTATGATGCTGACTATCCGGGTTGCGCTGGTACTGAGTTGCATCTGTCCGGCAAACTCCATTGATGGCAGGCCTCTTGCAGCTGCAGGAATTGTGGTTAGAGGAGACAAAGCCGTCAACATATACACCTCATCCCAGACAGGATCAATCATAGTTAAGCTCCTCCCGAATCTGCCCAAGGATAAGGAGGCATGTGCGAAAGCCCCCTTGGATGCATACAACAGGACATTGACCACTTTGCTCACCCCCCTTGGTGACTCTATCCGTAGGATACAAGAGTCTGTGACTACATCTGGAGGGCGGAGACAGAGGCGCTTTATAGGCGCCATTATTGGCGGTGTGGCTCTTGGGGTTGCAACTGCCGCACAAATAACAGCGGCCGCAGCTCTGATACAAGCCAAACAAAATGCTGCCAACATCCTCCGACTTAAAGAGAGCATTGCCGCAACCAATGAGGCTGTGCATGAGGTCACTGACGGATTATCGCAACTAGCAGTGGCAGTTGGGAAGATGCAGCAGTTTGTTAATGACCAATTTAATAAAACAGCTCAGGAATTAGACTGCATCAAAATTGCACAGCAAGTTGGTGTAGAGCTCAACCTGTACCTAACCGAATTGACTACAGTATTCGGACCACAAATCACTTCACCTGCTTTAAACAAGCTGACTATTCAGGCACTTTACAATCTAGCTGGTGGAAATATGGATTACTTATTGACTAAGTTAGGTGTAGGGAACAATCAACTCAGCTCATTAATCGGTAGCGGCTTAATCACtGGcAACCCTATTCTATACGACTCACAGACTCAACTCTTGGGTATACAGGTAACTgcaCCTTCAGTCGGGAACCTAAATAATATGCGTGCCACCTACTTGGAAACCTTATCCGTAAGCACAACCAGGGGATTTGCCTCGGCACTTGTCCCCAAAGTGGTGACACAGGTCGGTTCTGTGATAGAAGAACTTGACACCTCATACTGTATAGAAACTGACTTAGATTTATATTGTACAAGAATAGTAACGTTCCCTATGTCCCCTGGTATTTATTCCTGCTTGAGCGGCAATACGTCGGCCTGTATGTACTCAAAGACCGAAGGCGCACTTACTACACCATACATGACTATCAAAGGTTCAGTCATCGCCAACTGCAAGATGACAACATGTAGATGTGTAAACCCCCCGGGTATCATATCGCAAAACTATGGAGAAGCCGTGTCTCTAATAGATAAACAATCATGCAATGTTTTATCCTTAGGCGGGATAACTTTAAGGCTCAGTGGGGAATTCGATGTAACTTATCAGAAGAATATCTCAATACAAGATTCTCAAGTAATAATAACAGGCAATCTTGATATCTCAACTGAGCTTGGGAATGTCAACAACTCGATCAGTAATGCTTTGAATAAGTTAGAGGAAAGCAACAGAAAACTAGACAAAGTCAATGTCAAACTGACTAGCACATCTGCTCTCATTACgTATATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTGATTCTAGCATGCTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTTATTATGGCTTGGGAATAATACaCTcGATCAGATGAGAGCCACTACAAAAATGTGAACACAGATGAGGAACGAAGGTTTCCCTAATAGTAATTTGTGTGAAAGTTCTGGTAGTCTGTCAGTTCAGAGAGTTAAGAAAAAACTACCGGTTGTAGATGACCAAAGGACGATATACGGGTAGAACGGTAAGAGAGGCCGCCCCTCAATTGCGAGCCAGGCTTCACAACCTCCGTTCTACCGCTTCACCGACAACAGTCCTCAATCATGGACCGCGCCGTTAGCCAAGTTGCGTTAGAGAATGATGAAAGAGAGGCAAAAAATACATGGCGCTTGATATTCCGGATTGCAATCTTATTCTTAACAGTAGTGACCTTGGCTATATCTGTAGCCTCCCTTTTATATAGCATGGGGGCTAGCACACCTAGCGATCTTGTAGGCATACCGACTAGGATTTCCAGGGCAGAAGAAAAGATTACATCTACACTTGGTTCCAATCAAGATGTAGTAGATAGGATATATAAGCAAGTGGCCCTTGAGTCTCCGTTGGCATTGTTAAATACTGAGACCACAATTATGAACGCAATAACATCTCTCTCTTATCAGATTAATGGAGCTGCAAACAACAGTGGGTGGGGGGCACCTATCCATGACCCAGATTATATAGGGGGGATAGGCAAAGAACTCATTGTAGATGATGCTAGTGATGTCACATCATTCTATCCCTCTGCATTTCAAGAACATCTGAATTTTATCCCGGCGCCTACTACAGGATCAGGTTGCACTCGAATACCCTCATTTGACATGAGTGCTACCCATTACTGCTACACCCATAATGTAATATTGTCTGGATGCAGAGATCACTCACATTCATATCAGTATTTAGCACTTGGTGTGCTCCGGACATCTGCAACAGGGAGGGTATTCTTTTCTACTCTGCGTTCCATCAACCTGGACGACACCCAAAATCGGAAGTCTTGCAGTGTGAGTGCAACTCCCCTGGGTTGTGATATGCTGTGCTCGAAAGTCACGGAGACAGAGGAAGAAGATTATAACTCAGCTGTCCCTACGCGGATGGTACATGGGAGGTTAGGGTTCGACGGCCAGTACCACGAAAAGGACCTAGATGTCACAACATTATTCGGGGACTGGGTGGCCAACTACCCAGGAGTAGGGGGTGGATCTTTTATTGACAGCCGCGTATGGTTCTCAGTCTACGGAGGGTTAAAACCCAATTCACCCAGTGACACTGTACAGGAAGGGAAATATGTGATATACAAGCGATACAATGACACATGCCCAGATGAGCAAGACTACCAGATTCGAATGGCCAAGTCTTCGTATAAGCCTGGACGGTTTGGTGGGAAACGCATACAGCAGGCTATCTTATCTATCAAGGTGTCAACATCCTTAGGCGAAGACCCGGTACTGACTGTACCGCCCAACACAGTCACACTCATGGGGGCCGAAGGCAGAATTCTCACAGTAGGGACATCTCATTTCTTGTATCAACGAGGGTCATCATACTTCTCTCCCGCGTTATTATATCCTATGACAGTCAGCAACAAAACAGCCACTCTTCATAGTCCTTATACATTCAATGCCTTCACTCGGCCAGGTAGTATCCCTTGCCAGGCTTCAGCAAGATGCCCCAACTCGTGTGTTACTGGAGTCTATACAGATCCATATCCCCTAATCTTCTATAGAAACCACACCTTGCGAGGGGTATTCGGGACAATGCTTGATGGTGTACAAGCAAGACTTAACCCTGCGTCTGCAGTATTCGATAGCACATCCCGCAGTCGCATTACTCGAGTGAGTTCAAGCAGTACCAAAGCAGCATACACAACATCAACTTGTTTTAAAGTGGTCAAGACTAATAAGACCTATTGTCTCAGCATTGCTGAAATATCTAATACTCTCTTCGGAGAATTCAGAATCGTCCCGTTACTAGTTGAGATCCTCAAAGATGACGGGGTTAGAGAAGCCAGGTCTGGCTAGggcgcgccTTGAGTCAATTATAAAGGAGTTGGAAAGATGGCATTGTATCACCTATCTTCTGCGACATCAAGAATCAAACCGAATGCCGGCGCGTGCTCGAATTCCATGTTGCCAGTTGACCACAATCAGCCAGTGCTCATGCGATCAGATTAAGCCTTGTCATTAATCTCTTGATTAAGAAAAAATGTAAGTGGCAATGAGATACAAGGCAAAACAGCTCATGGTAAATAATACGGGTAGGACATGGCGAGCTCCGGTCCTGAAAGGGCAGAGCATCAGATTATCCTACCAGAGCCACACCTGTCTTCACCATTGGTCAAGCACAAACTACTCTATTACTGGAAATTAACTGGGCTACCGCTTCCTGATGAATGTGACTTCGACCACCTCATTCTCAGCCGACAATGGAAAAAAATACTTGAATCGGCCTCTCCTGATACTGAGAGAATGATAAAACTCGGAAGGGCAGTACACCAAACTCTTAACCACAATTCCAGAATAACCGGAGTGCTCCACCCCAGGTGTTTAGAACAACTGGCTAATATTGAGGTCCCAGATTCAACCAACAAATTTCGGAAGATTGAGAAGAAGATCCAAATTCACAACACGAGATATGGAGAACTGTTCACAAGGCTGTGTACGCATATAGAGAAGAAACTGCTGGGGTCATCTTGGTCTAACAATGTCCCCCGGTCAGAGGAGTTCAGCAGCATTCGTACGGATCCGGCATTCTGGTTTCACTCAAAATGGTCCACAGCCAAGTTTGCATGGCTCCATATAAAACAGATCCAGAGGCATCTGATGGTGGCAGCTAAGACAAGGTCTGCGGCCAACAAATTGGTGATGCTAACCCATAAGGTAGGCCAAGTCTTTGTCACTCCTGAACTTGTCGTTGTGACGCATACGAATGAGAACAAGTTCACATGTCTTACCCAGGAACTTGTATTGATGTATGCAGATATGATGGAGGGCAGAGATATGGTCAACATAATATCAACCACGGCGGTGCATCTCAGAAGCTTATCAGAGAAAATTGATGACATTTTGCGGTTAATAGACGCTCTGGCAAAAGACTTGGGTAATCAAGTCTACGATGTTGTATCACTAATGGAGGGATTTGCATACGGAGCTGTCCAGCTACTCGAGCCGTCAGGTACATTTGCAGGAGATTTCTTCGCATTCAACCTGCAGGAGCTTAAAGACATTCTAATTGGCCTCCTCCCCAATGATATAGCAGAATCCGTGACTCATGCAATCGCTACTGTATTCTCTGGTTTAGAACAGAATCAAGCAGCTGAGATGTTGTGTCTGTTGCGTCTGTGGGGTCACCCACTGCTTGAGTCCCGTATTGCAGCAAAGGCAGTCAGGAGCCAAATGTGCGCACCGAAAATGGTAGACTTTGATATGATCCTTCAGGTACTGTCTTTCTTCAAGGGAACAATCATCAACGGGTACAGAAAGAAGAATGCAGGTGTGTGGCCGCGAGTCAAAGTGGATACAATATATGGGAAGGTCATTGGGCAACTACATGCAGATTCAGCAGAGATTTCACACGATATCATGTTGAGAGAGTATAAGAGTTTATCTGCACTTGAATTTGAGCCATGTATAGAATATGACCCTGTCACCAACCTGAGCATGTTCCTAAAAGACAAGGCAATCGCACACCCCAACGATAATTGGCTTGCCTCGTTTAGGCGGAACCTTCTCTCCGAAGACCAGAAGAAACATGTAAAAGAAGCAACTTCGACTAATCGCCTCTTGATAGAGTTTTTAGAGTCAAATGATTTTGATCCATATAAAGAGATGGAATATCTGACGACCCTTGAGTACCTTAGAGATGACAATGTGGCAGTATCATACTCGCTCAAGGAGAAGGAAGTGAAAGTTAATGGACGGATCTTCGCTAAGCTGACAAAGAAGTTAAGGAACTGTCAGGTGATGGCGGAAGGGATCCTAGCCGATCAGATTGCACCTTTCTTTCAGGGAAATGGAGTCATTCAGGATAGCATATCCTTGACCAAGAGTATGCTAGCGATGAGTCAACTGTCTTTTAACAGCAATAAGAAACGTATCACTGACTGTAAAGAAAGAGTATCTTCAAACCGCAATCATGATCCGAAAAGCAAGAACCGTCGGAGAGTTGCAACCTTCATAACAACTGACCTGCAAAAGTACTGTCTTAATTGGAGATATCAGACAATCAAATTGTTCGCTCATGCCATCAATCAGTTGATGGGCCTACCTCACTTCTTCGAATGGATTCACCTAAGACTGATGGACACTACGATGTTCGTAGGAGACCCTTTCAATCCTCCAAGTGACCCTACTGACTGTGACCTCTCAAGAGTCCCTAATGATGACATATATATTGTCAGTGCCAGAGGGGGTATCGAAGGATTATGCCAGAAGCTATGGACAATGATCTCAATTGCTGCAATCCAACTTGCTGCAGCTAGATCGCATTGTCGTGTTGCCTGTATGGTACAGGGTGATAATCAAGTAATAGCAGTAACGAGAGAGGTAAGATCAGACGACTCTCCGGAGATGGTGTTGACACAGTTGCATCAAGCCAGTGATAATTTCTTCAAGGAATTAATTCATGTCAATCATTTGATTGGCCATAATTTGAAGGATCGTGAAACCATCAGGTCAGACACATTCTTCATATACAGCAAACGAATCTTCAAAGATGGAGCAATCCTCAGTCAAGTCCTCAAAAATTCATCTAAATTAGTGCTAGTGTCAGGTGATCTCAGTGAAAACACCGTAATGTCCTGTGCCAACATTGCCTCTACTGTAGCACGGCTATGCGAGAACGGGCTTCCCAAAGACTTCTGTTACTATTTAAACTATATAATGAGTTGTGTGCAGACATACTTTGACTCTGAGTTCTCCATCACCAACAATTCGCACCCCGATCTTAATCAGTCGTGGATTGAGGACATCTCTTTTGTGCACTCATATGTTCTGACTCCTGCCCAATTAGGGGGACTGAGTAACCTTCAATACTCAAGGCTCTACACTAGAAATATCGGTGACCCGGGGACTACTGCTTTTGCAGAGATCAAGCGACTAGAAGCAGTGGGATTACTGAGTCCTAACATTATGACTAATATCTTAACTAGGCCGCCTGGGAATGGAGATTGGGCCAGTCTGTGCAACGACCCATACTCTTTCAATTTTGAGACTGTTGCAAGCCCAAATATTGTTCTTAAGAAACATACGCAAAGAGTCCTATTTGAAACTTGTTCAAATCCCTTATTGTCTGGAGTGCACACAGAGGATAATGAGGCAGAAGAGAAGGCATTGGCTGAATTCTTGCTTAATCAAGAGGTGATTCATCCCCGCGTTGCGCATGCCATCATGGAGGCAAGCTCTGTAGGTAGGAGAAAGCAAATTCAAGGGCTTGTTGACACAACAAACACCGTAATTAAGATTGCGCTTACTAGGAGGCCATTAGGCATCAAGAGGCTGATGCGGATAGTCAATTATTCTAGCATGCATGCAATGCTGTTTAGAGACGATGTTTTTTCCTCCAGTAGATCCAACCACCCCTTAGTCTCTTCTAATATGTGTTCTCTGACACTGGCAGACTATGCACGGAATAGAAGCTGGTCACCTTTGACGGGAGGCAGGAAAATACTGGGTGTATCTAATCCTGATACGATAGAACTCGTAGAGGGTGAGATTCTTAGTGTAAGCGGAGGGTGTACAAGATGTGACAGCGGAGATGAACAATTTACTTGGTTCCATCTTCCAAGCAATATAGAATTGACCGATGACACCAGCAAGAATCCTCCGATGAGGGTACCATATCTCGGGTCAAAGACACAGGAGAGGAGAGCTGCCTCACTTGCAAAAATAGCTCATATGTCGCCACATGTAAAGGCTGCCCTAAGGGCATCATCCGTGTTGATCTGGGCTTATGGGGATAATGAAGTAAATTGGACTGCTGCTCTTACGATTGCAAAATCTCGGTGTAATGTAAACTTAGAGTATCTTCGGTTACTGTCCCCTTTACCCACGGCTGGGAATCTTCAACATAGACTAGATGATGGTATAACTCAGATGACATTCACCCCTGCATCTCTCTACAGGgtgtcaccttacattcacatatccaatgattctcaaaggctgttcactgaagaaggagtcaaagaggggaatgtggtttaccaacagatcATGCTCTTGGGTTTATCTCTAATCGAATCGATCTTTCCAATGACAACAACCAGGACATATGATGAGATCACACTGCACCTACATAGTAAATTTAGTTGCTGTATCAGAGAAGCACCTGTTGCGGTTCCTTTCGAGCTACTTGGGGTGGTACCGGAACTGAGGACAGTGACCTCAAATAAGTTTATGTATGATCCTAGCCCTGTATCGGAGGGAGACTTTGCGAGACTTGACTTAGCTATCTTCAAGAGTTATGAGCTTAATCTGGAGTCATATCCCACGATAGAGCTAATGAACATTCTTTCAATATCCAGCGGGAAGTTGATTGGCCAGTCTGTGGTTTCTTATGATGAAGATACCTCCATAAAGAATGACGCCATAATAGTGTATGACAATACCCGAAATTGGATCAGTGAAGCTCAGAATTCAGATGTGGTCCGCCTATTTGAATATGCAGCACTTGAAGTGCTCCTCGACTGTTCTTACCAACTCTATTACCTGAGAGTAAGAGGCCTAGACAATATTGTCTTATATATGGGTGATTTATACAAGAATATGCCAGGAATTCTACTTTCCAACATTGCAGCTACAATATCTCATCCCGTCATTCATTCAAGGTTACATGCAGTGGGCCTGGTCAACCATGACGGATCACACCAACTTGCAGATACGGATTTTATCGAAATGTCTGCAAAACTATTAGTATCTTGCACCCGACGTGTGATCTCCGGCTTATATTCAGGAAATAAGTATGATCTGCTGTTCCCATCTGTCTTAGATGATAACCTGAATGAGAAGATGCTTCAGCTGATATCCCGGTTATGCTGTCTGTACACGGTACTCTTTGCTACAACAAGAGAAATCCCGAAAATAAGAGGCTTAACTGCAGAAGAGAAATGTTCAATACTCACTGAGTATTTACTGTCGGATGCTGTGAAACCATTACTTAGCCCCGATCAAGTGAGCTCTATCATGTCTCCTAACATAATTACATTCCCAGCTAATCTGTACTACATGTCTCGGAAGAGCCTCAATTTGATCAGGGAAAGGGAGGACAGGGATACTATCCTGGCGTTGTTGTTCCCCCAAGAGCCATTATTAGAGTTCCCTTCTGTGCAAGATATTGGTGCTCGAGTGAAAGATCCATTCACCCGACAACCTGCGGCATTTTTGCAAGAGTTAGATTTGAGTGCTCCAGCAAGGTATGACGCATTCACACTTAGTCAGATTCATCCTGAACTCACATCTCCAAATCCGGAGGAAGACTACTTAGTACGATACTTGTTCAGAGGGATAGGGACTGCATCTTCCTCTTGGTATAAGGCATCTCATCTCCTTTCTGTACCCGAGGTAAGATGTGCAAGACACGGGAACTCCTTATACTTAGCTGAAGGGAGCGGAGCCATCATGAGTCTTCTCGAACTGCATGTACCACATGAAACTATCTATTACAATACGCTCTTTTCAAATGAGATGAACCCCCCGCAACGACATTTCGGGCCGACCCCAACTCAGTTTTTGAATTCGGTTGTTTATAGGAATCTACAGGCGGAGGTAACATGCAAAGATGGATTTGTCCAAGAGTTCCGTCCATTATGGAGAGAAAATACAGAGGAAAGTGACCTGACCTCAGATAAAGCAGTGGGGTATATTACATCTGCAGTGCCCTACAGATCTGTATCATTGCTGCATTGTGACATTGAAATTCCTCCAGGGTCCAATCAAAGCTTACTAGATCAACTAGCTATCAATTTATCTCTGATTGCCATGCATTCTGTAAGGGAGGGCGGGGTAGTAATCATCAAAGTGTTGTATGCAATGGGATACTACTTTCATCTACTCATGAACTTGTTTGCTCCGTGTTCCACAAAAGGATATATTCTCTCTAATGGTTATGCATGTCGAGGAGATATGGAGTGTTACCTGGTATTTGTCATGGGTTACCTGGGCGGGCCTACATTTGTACATGAGGTGGTGAGGATGGCAAAAACTCTGGTGCAGCGGCACGGTACGCTCTTGTCTAAATCAGATGAGATCACACTGACCAGGTTATTCACCTCACAGCGGCAGCGTGTGACAGACATCCTATCCAGTCCTTTACCAAGATTAATAAAGTACTTGAGGAAGAATATTGACACTGCGCTGATTGAAGCCGGGGGACAGCCCGTCCGTCCATTCTGTGCGGAGAGTCTGGTGAGCACGCTAGCGAACATAACTCAGATAACCCAGATTATCGCTAGTCACATTGACACAGTTATCCGGTCTGTGATATATATGGAAGCTGAGGGTGATCTCGCTGACACAGTATTTCTATTTACCCCTTACAATCTCTCTACTGACGGGAAAAAGAGGACATCACTTATACAGTGCACGAGACAGATCCTAGAGGTTACAATACTAGGTCTTAGAGTCGAAAATCTCAATAAAATAGGCGATATAATCAGCCTAGTGCTTAAAGGCATGATCTCCATGGAGGACCTTATCCCACTAAGGACATACTTGAAGCATAGTACCTGCCCTAAATATTTGAAGGCTGTCCTAGGTATTACCAAACTCAAAGAAATGTTTACAGACACTTCTGTATTGTACTTGACTCGTGCTCAACAAAAATTCTACATGAAAACTATAGGCAATGCAGTCAAAGGATATTACAGTAACTGTGACTCTTAACGAAAATCACATATTAATAGGCTCCTTTTTTGGCCAATTGTATTCTTGTTGATTTAATCATATTATGTTAGAAAAAAGTTGAACCCTGACTCCTTAGGACTCGAATTCGAACTCAAATAAATGTCTTAAAAAAAGGTTGCGCACAATTATTCTTGAGTGTAGTCTCGTCATTCACCAAATCTTTGTTTGGTGGCCGGCATGGTCCCAGCCTCCTCGCTGGCGCCGGCTGGGCAACATTCCGAGGGGACCGTCCCCTCGGTAATGGCGAATGGGACGTCGACTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTATA SEQ ID NO:GTTGGACCTTGGGTACGCGTTTATCATCAGCAGCAAGAGCCGCAAGAACAAC 24; reverseprimer for truncated form of the spike protein (SΔ19) SEQ ID NO:GGGAGACAGGGGCGCC 25; lentogenic nucleic acid sequence SEQ ID NO: GRQGRL26; lentogenic amino acid sequence SEQ ID NO:TAATACGACTCACTATAGGGACCAAACAGAGAATCCGTGAGTTACGATAAAAGGCGAAGG 27; NDV-AGCAATTGAAGTCGCACGGGTAGAAGGTGTGAATCTCGAGTGCGAGCCCGAAGCACAAAC F3 aaTCGAGAAAGCCTTCTGCCAACATGTCTTCCGTATTTGATGAGTACGAACAGCTCCTCGCG MolecularGCTCAGACTCGCCCCAATGGAGCTCATGGAGGGGGAGAAAAAGGGAGTACCTTAAAAGTA CloneGACGTCCCGGTATTCACTCTTAACAGTGATGACCCAGAAGATAGATGGAGCTTTGTGGTA AF077761.1_TTCTGCCTCCGGATTGCTGTTAGCGAAGATGCCAACAAACCACTCAGGCAAGGTGCTCTC LaSota_KanATATCTCTTTTATGCTCCCACTCACAGGTAATGAGGAACCATGTTGCCATTGCAGGGAAA R (withCAGAATGAAGCCACATTGGCCGTGCTTGAGATTGATGGCTTTGCCAACGGCACGCCCCAG stabilizingTTCAACAATAGGAGTGGAGTGTCTGAAGAGAGAGCACAGAGATTTGCGATGATAGCAGGA sequence inTCTCTCCCTCGGGCATGCAGCAACGGAACCCCGTTCGTCACAGCCGGGGCAGAAGATGAT L)GCACCAGAAGACATCACCGATACCCTGGAGAGGATCCTCTCTATCCAGGCTCAAGTATGG (mesogenic)GTCACAGTAGCAAAAGCCATGACTGCGTATGAGACTGCAGATGAGTCGGAAACAAGGCGAATCAATAAGTATATGCAGCAAGGCAGGGTCCAAAAGAAATACATCCTCTACCCCGTATGCAGGAGCACAATCCAACTCACGATCAGACAGTCTCTTGCAGTCCGCATCTTTTTGGTTAGCGAGCTCAAGAGAGGCCGCAACACGGCAGGTGGTACCTCTACTTATTATAACCTGGTAGGGGACGTAGACTCATACATCAGGAATACCGGGCTTACTGCATTCTTCTTGACACTCAAGTACGGAATCAACACCAAGACATCAGCCCTTGCACTTAGTAGCCTCTCAGGCGACATCCAGAAGATGAAGCAGCTCATGCGTTTGTATCGGATGAAAGGAGATAATGCGCCGTACATGACATTACTTGGTGATAGTGACCAGATGAGCTTTGCGCCTGCCGAGTATGCACAACTTTACTCCTTTGCCATGGGTATGGCATCAGTCCTAGATAAAGGTACTGGGAAATACCAATTTGCCAGGGACTTTATGAGCACATCATTCTGGAGACTTGGAGTAGAGTACGCTCAGGCTCAGGGAAGTAGCATTAACGAGGATATGGCTGCCGAGCTAAAGCTAACCCCAGCAGCAATGAAGGGCCTGGCAGCTGCTGCCCAACGGGTCTCCGACGATACCAGCAGCATATACATGCCTACTCAACAAGTCGGAGTCCTCACTGGGCTTAGCGAGGGGGGGTCCCAAGCTCTACAAGGCGGATCGAATAGATCGCAAGGGCAACCAGAAGCCGGGGATGGGGAGACCCAATTCCTGGATCTGATGAGAGCGGTAGCAAATAGCATGAGGGAGGCGCCAAACTCTGCACAGGGCACTCCCCAATCGGGGCCTCCCCCAACTCCTGGGCCATCCCAAGATAACGACACCGACTGGGGGTATTGATGGACAAAACCCAGCCTGCTTCCACAAAAACATCCCAATGCCCTCACCCGTAGTCGACCCCTCGATTTGCGGCTCTATATGACCACACCCTCAAACAAACATCCCCCTCTTTCCTCCCTCCCCCTGCTGTACAACTCCGCACGCCCTAGATACCACAGGCACAATGCGGCTCACTAACAATCAAAACAGAGCCGAGGGAATTAGAAAAAAGTACGGGTAGAAGAGGGATATTCAGAGATCAGGGCAAGTCTCCCGAGTCTCTGCTCTCTCCTCTACCTGATAGACCAGGACAAACATGGCCACCTTTACAGATGCAGAGATCGACGAGCTATTTGAGACAAGTGGAACTGTCATTGACAACATAATTACAGCCCAGGGTAAACCAGCAGAGACTGTTGGAAGGAGTGCAATCCCACAAGGCAAGACCAAGGTGCTGAGCGCAGCATGGGAGAAGCATGGGAGCATCCAGCCACCGGCCAGTCAAGACAACCCCGATCGACAGGACAGATCTGACAAACAACCATCCACACCCGAGCAAACGACCCCGCATGACAGCCCGCCGGCCACATCCGCCGACCAGCCCCCCACCCAGGCCACAGACGAAGCCGTCGACACACAGTTCAGGACCGGAGCAAGCAACTCTCTGCTGTTGATGCTTGACAAGCTCAGCAATAAATCGTCCAATGCTAAAAAGGGCCCATGGTCGAGCCCCCAAGAGGGGAATCACCAACGTCCGACTCAACAGCAGGGGAGTCAACCCAGTCGCGGAAACAGTCAGGAAAGACCGCAGAACCAAGTCAAGGCCGCCCCTGGAAACCAGGGCACAGACGTGAACACAGCATATCATGGACAATGGGAGGAGTCACAACTATCAGCTGGTGCAACCCCTCATGCTCTCCGATCAAGGCAGAGCCAAGACAATACCCTTGTATCTGCGGATCATGTCCAGCCACCTGTAGACTTTGTGCAAGCGATGATGTCTATGATGGAGGCGATATCACAGAGAGTAAGTAAGGTTGACTATCAGCTAGATCTTGTCTTGAAACAGACATCCTCCATCCCTATGATGCGGTCCGAAATCCAACAGCTGAAAACATCTGTTGCAGTCATGGAAGCCAACTTGGGAATGATGAAGATTCTGGATCCCGGTTGTGCCAACATTTCATCTCTGAGTGATCTACGGGCAGTTGCCCGATCTCACCCGGTTTTAGTTTCAGGCCCTGGAGACCCCTCTCCCTATGTGACACAAGGAGGCGAAATGGCACTTAATAAACTTTCGCAACCAGTGCCACATCCATCTGAATTGATTAAACCCGCCACTGCATGCGGGCCTGATATAGGAGTGGAAAAGGACACTGTCCGTGCATTGATCATGTCACGCCCAATGCACCCGAGTTCTTCAGCCAAGCTCCTAAGCAAGTTAGATGCAGCCGGGTCGATCGAGGAAATCAGGAAAATCAAGCGCCTTGCTCTAAATGGCTAATTACTACTGCCACACGTAGCGGGTCCCTGTCCACTCGGCATCACACGGAATCTGCACCGAGTTCCCCCtctagaggacgcgtACCCAAGGTCCAACTCTCCAAGCGGCAATCCTCTCTCGCTTCCTCAGCCCCACTGAATGGTCGCGTAACCGTAATTAATCTAGCTACATTTAAGATTAAGAAAAAATACGGGTAGAATTGGAGTGCCCCAATTGTGCCAAGATGGACTCATCTAGGACAATTGGGCTGTACTTTGATTCTGCCCATTCTTCTAGCAACCTGTTAGCATTTCCGATCGTCCTACAAGGCACAGGAGATGGGAAGAAGCAAATCGCCCCGCAATATAGGATCCAGCGCCTTGACTTGTGGACTGATAGTAAGGAGGACTCAGTATTCATCACCACCTATGGATTCATCTTTCAAGTTGGGAATGAAGAAGCCACTGTCGGCATGATCGATGATAAACCCAAGCGCGAGTTACTTTCCGCTGCGATGCTCTGCCTAGGAAGCGTCCCAAATACCGGAGACCTTATTGAGCTGGCAAGGGCCTGTCTCACTATGATAGTCACATGCAAGAAGAGTGCAACTAATACTGAGAGAATGGTTTTGTCAGTAGTGCAGGCACCCCAAGTGCTGCAAAGCTGTAGGGTTGTGGCAAACAAATACTCATCAGTGAATGCAGTCAAGCACGTGAAAGCGCCAGAGAAGATTCCCGGGAGTGGAACCCTAGAATACAAGGTGAACTTTGTCTCCTTGACTGTGGTACCGAAGAAGGATGTCTACAAGATCCCAGCTGCAGTATTGAAGGTTTCTGGCTCGAGTCTGTACAATCTTGCGCTCAATGTCACTATTAATGTGGAGGTAGACCCGAGGAGTCCTTTGGTTAAATCTTTGTCTAAGTCTGACAGCGGATACTATGCTAACCTCTTCTTGCATATTGGACTTATGACCACCGTAGATAGGAAGGGGAAGAAAGTGACATTTGACAAGCTGGAAAAGAAAATAAGGAGCCTTGATCTATCTGTCGGGCTCAGTGATGTGCTCGGGCCTTCCGTGTTGGTAAAAGCAAGAGGTGCACGGACTAAGCTTTTGGCACCTTTCTTCTCTAGCAGTGGGACAGCCTGCTATCCCATAGCAAATGCTTCTCCTCAGGTGGCCAAGATACTCTGGAGTCAAACCGCGTGCCTGCGGAGCGTTAAAATCATTATCCAAGCAGGTACCCAACGCGCTGTCGCAGTGACCGCCGACCACGAGGTTACCTCTACTAAGCTGGAGAAGGGGCACACCCTTGCCAAATACAATCCTTTTAAGAAATAAGCTGCGTCTCTGAGATTGCGCTCCGCCCACTCACCCAGATCATCATGACACAAAAAACTAATCTGTCTTGATTATTTACAGTTAGTTTACCTGTCTATCAAGTTAGAAAAAACACGGGTAGAAGATTCTGGATCCCGGTTGGCGCCCTCCAGGTGCAAGttaattaaATGGGCTCCAGACCTTCTACCAAGAACCCAGCACCTATGATGCTGACTATCCGGGTTGCGCTGGTACTGAGTTGCATCTGTCCGGCAAACTCCATTGATGGCAGGCCTCTTGCAGCTGCAGGAATTGTGGTTACAGGAGACAAAGCCGTCAACATATACACCTCATCCCAGACAGGATCAATCATAGTTAAGCTCCTCCCGAATCTGCCCAAGGATAAGGAGGCATGTGCGAAAGCCCCCTTGGATGCATACAACAGGACATTGACCACTTTGCTCACCCCCCTTGGTGACTCTATCCGTAGGATACAAGAGTCTGTGACTACATCTGGAGGGCGGAGACAGAGGCGCTTTATAGGCGCCATTATTGGCGGTGTGGCTCTTGGGGTTGCAACTGCCGCACAAATAACAGCGGCCGCAGCTCTGATACAAGCCAAACAAAATGCTGCCAACATCCTCCGACTTAAAGAGAGCATTGCCGCAACCAATGAGGCTGTGCATGAGGTCACTGACGGATTATCGCAACTAGCAGTGGCAGTTGGGAAGATGCAGCAGTTTGTTAATGACCAATTTAATAAAACAGCTCAGGAATTAGACTGCATCAAAATTGCACAGCAAGTTGGTGTAGAGCTCAACCTGTACCTAACCGAATTGACTACAGTATTCGGACCACAAATCACTTCACCTGCTTTAAACAAGCTGACTATTCAGGCACTTTACAATCTAGCTGGTGGAAATATGGATTACTTATTGACTAAGTTAGGTGTAGGGAACAATCAACTCAGCTCATTAATCGGTAGCGGCTTAATCACtGGCAACCCTATTCTATACGACTCACAGACTCAACTCTTGGGTATACAGGTAACTgCaCCTTCAGTCGGGAACCTAAATAATATGCGTGCCACCTACTTGGAAACCTTATCCGTAAGCACAACCAGGGGATTTGCCTCGGCACTTGTCCCCAAAGTGGTGACACAGGTCGGTTCTGTGATAGAAGAACTTGACACCTCATACTGTATAGAAACTGACTTAGATTTATATTGTACAAGAATAGTAACGTTCCCTATGTCCCCTGGTATTTATTCCTGCTTGAGCGGCAATACGTCGGCCTGTATGTACTCAAAGACCGAAGGCGCACTTACTACACCATACATGACTATCAAAGGTTCAGTCATCGCCAACTGCAAGATGACAACATGTAGATGTGTAAACCCCCCGGGTATCATATCGCAAAACTATGGAGAAGCCGTGTCTCTAATAGATAAACAATCATGCAATGTTTTATCCTTAGGCGGGATAACTTTAAGGCTCAGTGGGGAATTCGATGTAACTTATCAGAAGAATATCTCAATACAAGATTCTCAAGTAATAATAACAGGCAATCTTGATATCTCAACTGAGCTTGGGAATGTCAACAACTCGATCAGTAATGCTTTGAATAAGTTAGAGGAAAGCAACAGAAAACTAGACAAAGTCAATGTCAAACTGACTAGCACATCTGCTCTCATTACgTATATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTGATTCTAGCATGCTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTTATTATGGCTTGGGAATAATACaCTcGATCAGATGAGAGCCACTACAAAAATGTGAACACAGATGAGGAACGAAGGTTTCCCTAATAGTAATTTGTGTGAAAGTTCTGGTAGTCTGTCAGTTCAGAGAGTTAAGAAAAAACTACCGGTTGTAGATGACCAAAGGACGATATACGGGTAGAACGGTAAGAGAGGCCGCCCCTCAATTGCGAGCCAGGCTTCACAACCTCCGTTCTACCGCTTCACCGACAACAGTCCTCAATCATGGACCGCGCCGTTAGCCAAGTTGCGTTAGAGAATGATGAAAGAGAGGCAAAAAATACATGGCGCTTGATATTCCGGATTGCAATCTTATTCTTAACAGTAGTGACCTTGGCTATATCTGTAGCCTCCCTTTTATATAGCATGGGGGCTAGCACACCTAGCGATCTTGTAGGCATACCGACTAGGATTTCCAGGGCAGAAGAAAAGATTACATCTACACTTGGTTCCAATCAAGATGTAGTAGATAGGATATATAAGCAAGTGGCCCTTGAGTCTCCGTTGGCATTGTTAAATACTGAGACCACAATTATGAACGCAATAACATCTCTCTCTTATCAGATTAATGGAGCTGCAAACAACAGTGGGTGGGGGGCACCTATCCATGACCCAGATTATATAGGGGGGATAGGCAAAGAACTCATTGTAGATGATGCTAGTGATGTCACATCATTCTATCCCTCTGCATTTCAAGAACATCTGAATTTTATCCCGGCGCCTACTACAGGATCAGGTTGCACTCGAATACCCTCATTTGACATGAGTGCTACCCATTACTGCTACACCCATAATGTAATATTGTCTGGATGCAGAGATCACTCACATTCATATCAGTATTTAGCACTTGGTGTGCTCCGGACATCTGCAACAGGGAGGGTATTCTTTTCTACTCTGCGTTCCATCAACCTGGACGACACCCAAAATCGGAAGTCTTGCAGTGTGAGTGCAACTCCCCTGGGTTGTGATATGCTGTGCTCGAAAGTCACGGAGACAGAGGAAGAAGATTATAACTCAGCTGTCCCTACGCGGATGGTACATGGGAGGTTAGGGTTCGACGGCCAGTACCACGAAAAGGACCTAGATGTCACAACATTATTCGGGGACTGGGTGGCCAACTACCCAGGAGTAGGGGGTGGATCTTTTATTGACAGCCGCGTATGGTTCTCAGTCTACGGAGGGTTAAAACCCAATTCACCCAGTGACACTGTACAGGAAGGGAAATATGTGATATACAAGCGATACAATGACACATGCCCAGATGAGCAAGACTACCAGATTCGAATGGCCAAGTCTTCGTATAAGCCTGGACGGTTTGGTGGGAAACGCATACAGCAGGCTATCTTATCTATCAAGGTGTCAACATCCTTAGGCGAAGACCCGGTACTGACTGTACCGCCCAACACAGTCACACTCATGGGGGCCGAAGGCAGAATTCTCACAGTAGGGACATCTCATTTCTTGTATCAACGAGGGTCATCATACTTCTCTCCCGCGTTATTATATCCTATGACAGTCAGCAACAAAACAGCCACTCTTCATAGTCCTTATACATTCAATGCCTTCACTCGGCCAGGTAGTATCCCTTGCCAGGCTTCAGCAAGATGCCCCAACTCGTGTGTTACTGGAGTCTATACAGATCCATATCCCCTAATCTTCTATAGAAACCACACCTTGCGAGGGGTATTCGGGACAATGCTTGATGGTGTACAAGCAAGACTTAACCCTGCGTCTGCAGTATTCGATAGCACATCCCGCAGTCGCATTACTCGAGTGAGTTCAAGCAGTACCAAAGCAGCATACACAACATCAACTTGTTTTAAAGTGGTCAAGACTAATAAGACCTATTGTCTCAGCATTGCTGAAATATCTAATACTCTCTTCGGAGAATTCAGAATCGTCCCGTTACTAGTTGAGATCCTCAAAGATGACGGGGTTAGAGAAGCCAGGTCTGGCTAGggcgcgccTTGAGTCAATTATAAAGGAGTTGGAAAGATGGCATTGTATCACCTATCTTCTGCGACATCAAGAATCAAACCGAATGCCGGCGCGTGCTCGAATTCCATGTTGCCAGTTGACCACAATCAGCCAGTGCTCATGCGATCAGATTAAGCCTTGTCATTAATCTCTTGATTAAGAAAAAATGTAAGTGGCAATGAGATACAAGGCAAAACAGCTCATGGTAAATAATACGGGTAGGACATGGCGAGCTCCGGTCCTGAAAGGGCAGAGCATCAGATTATCCTACCAGAGCCACACCTGTCTTCACCATTGGTCAAGCACAAACTACTCTATTACTGGAAATTAACTGGGCTACCGCTTCCTGATGAATGTGACTTCGACCACCTCATTCTCAGCCGACAATGGAAAAAAATACTTGAATCGGCCTCTCCTGATACTGAGAGAATGATAAAACTCGGAAGGGCAGTACACCAAACTCTTAACCACAATTCCAGAATAACCGGAGTGCTCCACCCCAGGTGTTTAGAACAACTGGCTAATATTGAGGTCCCAGATTCAACCAACAAATTTCGGAAGATTGAGAAGAAGATCCAAATTCACAACACGAGATATGGAGAACTGTTCACAAGGCTGTGTACGCATATAGAGAAGAAACTGCTGGGGTCATCTTGGTCTAACAATGTCCCCCGGTCAGAGGAGTTCAGCAGCATTCGTACGGATCCGGCATTCTGGTTTCACTCAAAATGGTCCACAGCCAAGTTTGCATGGCTCCATATAAAACAGATCCAGAGGCATCTGATGGTGGCAGCTAAGACAAGGTCTGCGGCCAACAAATTGGTGATGCTAACCCATAAGGTAGGCCAAGTCTTTGTCACTCCTGAACTTGTCGTTGTGACGCATACGAATGAGAACAAGTTCACATGTCTTACCCAGGAACTTGTATTGATGTATGCAGATATGATGGAGGGCAGAGATATGGTCAACATAATATCAACCACGGCGGTGCATCTCAGAAGCTTATCAGAGAAAATTGATGACATTTTGCGGTTAATAGACGCTCTGGCAAAAGACTTGGGTAATCAAGTCTACGATGTTGTATCACTAATGGAGGGATTTGCATACGGAGCTGTCCAGCTACTCGAGCCGTCAGGTACATTTGCAGGAGATTTCTTCGCATTCAACCTGCAGGAGCTTAAAGACATTCTAATTGGCCTCCTCCCCAATGATATAGCAGAATCCGTGACTCATGCAATCGCTACTGTATTCTCTGGTTTAGAACAGAATCAAGCAGCTGAGATGTTGTGTCTGTTGCGTCTGTGGGGTCACCCACTGCTTGAGTCCCGTATTGCAGCAAAGGCAGTCAGGAGCCAAATGTGCGCACCGAAAATGGTAGACTTTGATATGATCCTTCAGGTACTGTCTTTCTTCAAGGGAACAATCATCAACGGGTACAGAAAGAAGAATGCAGGTGTGTGGCCGCGAGTCAAAGTGGATACAATATATGGGAAGGTCATTGGGCAACTACATGCAGATTCAGCAGAGATTTCACACGATATCATGTTGAGAGAGTATAAGAGTTTATCTGCACTTGAATTTGAGCCATGTATAGAATATGACCCTGTCACCAACCTGAGCATGTTCCTAAAAGACAAGGCAATCGCACACCCCAACGATAATTGGCTTGCCTCGTTTAGGCGGAACCTTCTCTCCGAAGACCAGAAGAAACATGTAAAAGAAGCAACTTCGACTAATCGCCTCTTGATAGAGTTTTTAGAGTCAAATGATTTTGATCCATATAAAGAGATGGAATATCTGACGACCCTTGAGTACCTTAGAGATGACAATGTGGCAGTATCATACTCGCTCAAGGAGAAGGAAGTGAAAGTTAATGGACGGATCTTCGCTAAGCTGACAAAGAAGTTAAGGAACTGTCAGGTGATGGCGGAAGGGATCCTAGCCGATCAGATTGCACCTTTCTTTCAGGGAAATGGAGTCATTCAGGATAGCATATCCTTGACCAAGAGTATGCTAGCGATGAGTCAACTGTCTTTTAACAGCAATAAGAAACGTATCACTGACTGTAAAGAAAGAGTATCTTCAAACCGCAATCATGATCCGAAAAGCAAGAACCGTCGGAGAGTTGCAACCTTCATAACAACTGACCTGCAAAAGTACTGTCTTAATTGGAGATATCAGACAATCAAATTGTTCGCTCATGCCATCAATCAGTTGATGGGCCTACCTCACTTCTTCGAATGGATTCACCTAAGACTGATGGACACTACGATGTTCGTAGGAGACCCTTTCAATCCTCCAAGTGACCCTACTGACTGTGACCTCTCAAGAGTCCCTAATGATGACATATATATTGTCAGTGCCAGAGGGGGTATCGAAGGATTATGCCAGAAGCTATGGACAATGATCTCAATTGCTGCAATCCAACTTGCTGCAGCTAGATCGCATTGTCGTGTTGCCTGTATGGTACAGGGTGATAATCAAGTAATAGCAGTAACGAGAGAGGTAAGATCAGACGACTCTCCGGAGATGGTGTTGACACAGTTGCATCAAGCCAGTGATAATTTCTTCAAGGAATTAATTCATGTCAATCATTTGATTGGCCATAATTTGAAGGATCGTGAAACCATCAGGTCAGACACATTCTTCATATACAGCAAACGAATCTTCAAAGATGGAGCAATCCTCAGTCAAGTCCTCAAAAATTCATCTAAATTAGTGCTAGTGTCAGGTGATCTCAGTGAAAACACCGTAATGTCCTGTGCCAACATTGCCTCTACTGTAGCACGGCTATGCGAGAACGGGCTTCCCAAAGACTTCTGTTACTATTTAAACTATATAATGAGTTGTGTGCAGACATACTTTGACTCTGAGTTCTCCATCACCAACAATTCGCACCCCGATCTTAATCAGTCGTGGATTGAGGACATCTCTTTTGTGCACTCATATGTTCTGACTCCTGCCCAATTAGGGGGACTGAGTAACCTTCAATACTCAAGGCTCTACACTAGAAATATCGGTGACCCGGGGACTACTGCTTTTGCAGAGATCAAGCGACTAGAAGCAGTGGGATTACTGAGTCCTAACATTATGACTAATATCTTAACTAGGCCGCCTGGGAATGGAGATTGGGCCAGTCTGTGCAACGACCCATACTCTTTCAATTTTGAGACTGTTGCAAGCCCAAATATTGTTCTTAAGAAACATACGCAAAGAGTCCTATTTGAAACTTGTTCAAATCCCTTATTGTCTGGAGTGCACACAGAGGATAATGAGGCAGAAGAGAAGGCATTGGCTGAATTCTTGCTTAATCAAGAGGTGATTCATCCCCGCGTTGCGCATGCCATCATGGAGGCAAGCTCTGTAGGTAGGAGAAAGCAAATTCAAGGGCTTGTTGACACAACAAACACCGTAATTAAGATTGCGCTTACTAGGAGGCCATTAGGCATCAAGAGGCTGATGCGGATAGTCAATTATTCTAGCATGCATGCAATGCTGTTTAGAGACGATGTTTTTTCCTCCAGTAGATCCAACCACCCCTTAGTCTCTTCTAATATGTGTTCTCTGACACTGGCAGACTATGCACGGAATAGAAGCTGGTCACCTTTGACGGGAGGCAGGAAAATACTGGGTGTATCTAATCCTGATACGATAGAACTCGTAGAGGGTGAGATTCTTAGTGTAAGCGGAGGGTGTACAAGATGTGACAGCGGAGATGAACAATTTACTTGGTTCCATCTTCCAAGCAATATAGAATTGACCGATGACACCAGCAAGAATCCTCCGATGAGGGTACCATATCTCGGGTCAAAGACACAGGAGAGGAGAGCTGCCTCACTTGCAAAAATAGCTCATATGTCGCCACATGTAAAGGCTGCCCTAAGGGCATCATCCGTGTTGATCTGGGCTTATGGGGATAATGAAGTAAATTGGACTGCTGCTCTTACGATTGCAAAATCTCGGTGTAATGTAAACTTAGAGTATCTTCGGTTACTGTCCCCTTTACCCACGGCTGGGAATCTTCAACATAGACTAGATGATGGTATAACTCAGATGACATTCACCCCTGCATCTCTCTACAGGgtgtcaccttacattcacatatccaatgattctcaaaggctgttcactgaagaaggagtcaaagaggggaatgtggtttaccaacagatcATGCTCTTGGGTTTATCTCTAATCGAATCGATCTTTCCAATGACAACAACCAGGACATATGATGAGATCACACTGCACCTACATAGTAAATTTAGTTGCTGTATCAGAGAAGCACCTGTTGCGGTTCCTTTCGAGCTACTTGGGGTGGTACCGGAACTGAGGACAGTGACCTCAAATAAGTTTATGTATGATCCTAGCCCTGTATCGGAGGGAGACTTTGCGAGACTTGACTTAGCTATCTTCAAGAGTTATGAGCTTAATCTGGAGTCATATCCCACGATAGAGCTAATGAACATTCTTTCAATATCCAGCGGGAAGTTGATTGGCCAGTCTGTGGTTTCTTATGATGAAGATACCTCCATAAAGAATGACGCCATAATAGTGTATGACAATACCCGAAATTGGATCAGTGAAGCTCAGAATTCAGATGTGGTCCGCCTATTTGAATATGCAGCACTTGAAGTGCTCCTCGACTGTTCTTACCAACTCTATTACCTGAGAGTAAGAGGCCTAGACAATATTGTCTTATATATGGGTGATTTATACAAGAATATGCCAGGAATTCTACTTTCCAACATTGCAGCTACAATATCTCATCCCGTCATTCATTCAAGGTTACATGCAGTGGGCCTGGTCAACCATGACGGATCACACCAACTTGCAGATACGGATTTTATCGAAATGTCTGCAAAACTATTAGTATCTTGCACCCGACGTGTGATCTCCGGCTTATATTCAGGAAATAAGTATGATCTGCTGTTCCCATCTGTCTTAGATGATAACCTGAATGAGAAGATGCTTCAGCTGATATCCCGGTTATGCTGTCTGTACACGGTACTCTTTGCTACAACAAGAGAAATCCCGAAAATAAGAGGCTTAACTGCAGAAGAGAAATGTTCAATACTCACTGAGTATTTACTGTCGGATGCTGTGAAACCATTACTTAGCCCCGATCAAGTGAGCTCTATCATGTCTCCTAACATAATTACATTCCCAGCTAATCTGTACTACATGTCTCGGAAGAGCCTCAATTTGATCAGGGAAAGGGAGGACAGGGATACTATCCTGGCGTTGTTGTTCCCCCAAGAGCCATTATTAGAGTTCCCTTCTGTGCAAGATATTGGTGCTCGAGTGAAAGATCCATTCACCCGACAACCTGCGGCATTTTTGCAAGAGTTAGATTTGAGTGCTCCAGCAAGGTATGACGCATTCACACTTAGTCAGATTCATCCTGAACTCACATCTCCAAATCCGGAGGAAGACTACTTAGTACGATACTTGTTCAGAGGGATAGGGACTGCATCTTCCTCTTGGTATAAGGCATCTCATCTCCTTTCTGTACCCGAGGTAAGATGTGCAAGACACGGGAACTCCTTATACTTAGCTGAAGGGAGCGGAGCCATCATGAGTCTTCTCGAACTGCATGTACCACATGAAACTATCTATTACAATACGCTCTTTTCAAATGAGATGAACCCCCCGCAACGACATTTCGGGCCGACCCCAACTCAGTTTTTGAATTCGGTTGTTTATAGGAATCTACAGGCGGAGGTAACATGCAAAGATGGATTTGTCCAAGAGTTCCGTCCATTATGGAGAGAAAATACAGAGGAAAGTGACCTGACCTCAGATAAAGCAGTGGGGTATATTACATCTGCAGTGCCCTACAGATCTGTATCATTGCTGCATTGTGACATTGAAATTCCTCCAGGGTCCAATCAAAGCTTACTAGATCAACTAGCTATCAATTTATCTCTGATTGCCATGCATTCTGTAAGGGAGGGCGGGGTAGTAATCATCAAAGTGTTGTATGCAATGGGATACTACTTTCATCTACTCATGAACTTGTTTGCTCCGTGTTCCACAAAAGGATATATTCTCTCTAATGGTTATGCATGTCGAGGAGATATGGAGTGTTACCTGGTATTTGTCATGGGTTACCTGGGCGGGCCTACATTTGTACATGAGGTGGTGAGGATGGCAAAAACTCTGGTGCAGCGGCACGGTACGCTCTTGTCTAAATCAGATGAGATCACACTGACCAGGTTATTCACCTCACAGCGGCAGCGTGTGACAGACATCCTATCCAGTCCTTTACCAAGATTAATAAAGTACTTGAGGAAGAATATTGACACTGCGCTGATTGAAGCCGGGGGACAGCCCGTCCGTCCATTCTGTGCGGAGAGTCTGGTGAGCACGCTAGCGAACATAACTCAGATAACCCAGATTATCGCTAGTCACATTGACACAGTTATCCGGTCTGTGATATATATGGAAGCTGAGGGTGATCTCGCTGACACAGTATTTCTATTTACCCCTTACAATCTCTCTACTGACGGGAAAAAGAGGACATCACTTATACAGTGCACGAGACAGATCCTAGAGGTTACAATACTAGGTCTTAGAGTCGAAAATCTCAATAAAATAGGCGATATAATCAGCCTAGTGCTTAAAGGCATGATCTCCATGGAGGACCTTATCCCACTAAGGACATACTTGAAGCATAGTACCTGCCCTAAATATTTGAAGGCTGTCCTAGGTATTACCAAACTCAAAGAAATGTTTACAGACACTTCTGTATTGTACTTGACTCGTGCTCAACAAAAATTCTACATGAAAACTATAGGCAATGCAGTCAAAGGATATTACAGTAACTGTGACTCTTAACGAAAATCACATATTAATAGGCTCCTTTTTTGGCCAATTGTATTCTTGTTGATTTAATCATATTATGTTAGAAAAAAGTTGAACCCTGACTCCTTAGGACTCGAATTCGAACTCAAATAAATGTCTTAAAAAAAGGTTGCGCACAATTATTCTTGAGTGTAGTCTCGTCATTCACCAAATCTTTGTTTGGTGGCCGGCATGGTCCCAGCCTCCTCGCTGGCGCCGGCTGGGCAACATTCCGAGGGGACCGTCCCCTCGGTAATGGCGAATGGGACGTCGACTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTATA SEQ ID NO:MGSRPSTKNPAPMMLTIRVALVLSCICPANSIDGRPLAAAGIVVTGDKAVNIYTSSQTGS 28; NDV FIIVKLLPNLPKDKEACAKAPLDAYNRTLTTLLTPLGDSIRRIQESVTTSGGGRQGRLIGAgene wildtypeIIGGVALGVATAAQITAAAALIQAKQNAANILRLKESIAATNEAVHEVTDGLSQLAVAVG(lentogenic)KMQQFVNDQFNKTAQELDCIKIAQQVGVELNLYLTELTTVFGPQITSPALNKLTIQALYN (553 aa)LAGGNMDYLLTKLGVGNNQLSSLIGSGLITGNPILYDSQTQLLGIQVTAPSVGNLNNMRATYLETLSVSTTRGFASALVPKVVTQVGSVIEELDTSYCIETDLDLYCTRIVTFPMSPGIYSCLSGNTSACMYSKTEGALTTPYMTIKGSVIANCKMTTCRCVNPPGIISQNYGEAVSLIDKQSCNVLSLGGITLRLSGEFDVTYQKNISIQDSQVIITGNLDISTELGNVNNSISNALNKLEESNRKLDKVNVKLTSTSALITYIVLTIISLVFGILSLILACYLMYKQKAQQKTLLWLGNNTLDQMRATTKM SEQ ID NO:MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS 29; B117NVTWFHAISGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNspike proteinATNVVIKVCEFQFCNDPFLGVYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGGVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTYGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIDDTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQGVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSHRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPINFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILARLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTHNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEP VLKGVKLHYTSEQ ID NO: MFVFLVLLPLVSSQCVNFTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS30; B1.351 NVTWFHAIHVSGTNGTKRFANPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVspike proteinNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRGLPQGFSALEPLVDLPIGINITRFQTLHISYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGNIADYNYKLPDDFTGGVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVKGFNCYFPLQSYGFQPTYGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQGVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGVENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEP VLKGVKLHYTSEQ ID NO: MFVFLVLLPLVSSQCVNFTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS31; NVTWFHAIHVSGTNGTKRFANPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVB1.351PP NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEspike proteinGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRGLPQGFSALEPLVDLPIGINITRFQTLHISYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGNIADYNYKLPDDFTGGVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVKGFNCYFPLQSYGFQPTYGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQGVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGVENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEP VLKGVKLHYTSEQ ID NO: ATGGGCTCCAGACCTTCTACCAAGAACCCAGCACCTATGATGCTGACTATCCGGGTTGCG32; NDV wildCTGGTACTGAGTTGCATCTGTCCGGCAAACTCCATTGATGGCAGGCCTCTTGCAGCTGCA type F geneGGAATTGTGGTTACAGGAGACAAAGCCGTCAACATATACACCTCATCCCAGACAGGATCA fromATCATAGTTAAGCTCCTCCCGAATCTGCCCAAGGATAAGGAGGCATGTGCGAAAGCCCCC accession #TTGGATGCATACAACAGGACATTGACCACTTTGCTCACCCCCCTTGGTGACTCTATCCGT AF077761.1AGGATACAAGAGTCTGTGACTACATCTGGAGGGGGGAGACAGGGGCGCCTTATAGGCGCCATTATTGGCGGTGTGGCTCTTGGGGTTGCAACTGCCGCACAAATAACAGCGGCCGCAGCTCTGATACAAGCCAAACAAAATGCTGCCAACATCCTCCGACTTAAAGAGAGCATTGCCGCAACCAATGAGGCTGTGCATGAGGTCACTGACGGATTATCGCAACTAGCAGTGGCAGTTGGGAAGATGCAGCAGTTTGTTAATGACCAATTTAATAAAACAGCTCAGGAATTAGACTGCATCAAAATTGCACAGCAAGTTGGTGTAGAGCTCAACCTGTACCTAACCGAATTGACTACAGTATTCGGACCACAAATCACTTCACCTGCTTTAAACAAGCTGACTATTCAGGCACTTTACAATCTAGCTGGTGGAAATATGGATTACTTATTGACTAAGTTAGGTGTAGGGAACAATCAACTCAGCTCATTAATCGGTAGCGGCTTAATCACtGGcAACCCTATTCTATACGACTCACAGACTCAACTCTTGGGTATACAGGTAACTgcaCCTTCAGTCGGGAACCTAAATAATATGCGTGCCACCTACTTGGAAACCTTATCCGTAAGCACAACCAGGGGATTTGCCTCGGCACTTGTCCCCAAAGTGGTGACACAGGTCGGTTGTGTGATAGAAGAACTTGACACCTCATACTGTATAGAAACTGACTTAGATTTATATTGTACAAGAATAGTAACGTTCCCTATGTCCCCTGGTATTTATTCCTGCTTGAGCGGCAATACGTCGGCCTGTATGTACTCAAAGACCGAAGGCGCACTTACTACACCATACATGACTATCAAAGGTTCAGTCATCGCCAACTGCAAGATGACAACATGTAGATGTGTAAACCCCCCGGGTATCATATCGCAAAACTATGGAGAAGCCGTGTCTCTAATAGATAAACAATCATGCAATGTTTTATCCTTAGGCGGGATAACTTTAAGGCTCAGTGGGGAATTCGATGTAACTTATCAGAAGAATATCTCAATACAAGATTCTCAAGTAATAATAACAGGCAATCTTGATATCTCAACTGAGCTTGGGAATGTCAACAACTCGATCAGTAATGCTTTGAATAAGTTAGAGGAAAGCAACAGAAAACTAGACAAAGTCAATGTCAAACTGACTAGCACATCTGCTCTCATTACgTATATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTGATTCTAGCATGCTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTTATTATGGCTTGGGAATAATACaCTcGATCAGATGAGAGCCACTACAAAAATGTGA SEQ ID NO:ATGGACCGCGCCGTTAGCCAAGTTGCGTTAGAGAATGATGAAAGAGAGGCAAAAAATACA33; NDV wildTGGCGCTTGATATTCCGGATTGCAATCTTATTCTTAACAGTAGTGACCTTGGCTATATCTtype HN geneGTAGCCTCCCTTTTATATAGCATGGGGGCTAGCACACCTAGCGATCTTGTAGGCATACCG fromACTAGGATTTCCAGGGCAGAAGAAAAGATTACATCTACACTTGGTTCCAATCAAGATGTA accession #GTAGATAGGATATATAAGCAAGTGGCCCTTGAGTCTCCGTTGGCATTGTTAAATACTGAG AF077761.1ACCACAATTATGAACGCAATAACATCTCTCTCTTATCAGATTAATGGAGCTGCAAACAACAGTGGGTGGGGGGCACCTATCCATGACCCAGATTATATAGGGGGGATAGGCAAAGAACTCATTGTAGATGATGCTAGTGATGTCACATCATTCTATCCCTCTGCATTTCAAGAACATCTGAATTTTATCCCGGCGCCTACTACAGGATCAGGTTGCACTCGAATACCCTCATTTGACATGAGTGCTACCCATTACTGCTACACCCATAATGTAATATTGTCTGGATGCAGAGATCACTCACATTCATATCAGTATTTAGCACTTGGTGTGCTCCGGACATCTGCAACAGGGAGGGTATTCTTTTCTACTCTGCGTTCCATCAACCTGGACGACACCCAAAATCGGAAGTCTTGCAGTGTGAGTGCAACTCCCCTGGGTTGTGATATGCTGTGCTCGAAAGTCACGGAGACAGAGGAAGAAGATTATAACTCAGCTGTCCCTACGCGGATGGTACATGGGAGGTTAGGGTTCGACGGCCAGTACCACGAAAAGGACCTAGATGTCACAACATTATTCGGGGACTGGGTGGCCAACTACCCAGGAGTAGGGGGTGGATCTTTTATTGACAGCCGCGTATGGTTCTCAGTCTACGGAGGGTTAAAACCCAATTCACCCAGTGACACTGTACAGGAAGGGAAATATGTGATATACAAGCGATACAATGACACATGCCCAGATGAGCAAGACTACCAGATTCGAATGGCCAAGTCTTCGTATAAGCCTGGACGGTTTGGTGGGAAACGCATACAGCAGGCTATCTTATCTATCAAGGTGTCAACATCCTTAGGCGAAGACCCGGTACTGACTGTACCGCCCAACACAGTCACACTCATGGGGGCCGAAGGCAGAATTCTCACAGTAGGGACATCTCATTTCTTGTATCAACGAGGGTCATCATACTTCTCTCCCGCGTTATTATATCCTATGACAGTCAGCAACAAAACAGCCACTCTTCATAGTCCTTATACATTCAATGCCTTCACTCGGCCAGGTAGTATCCCTTGCCAGGCTTCAGCAAGATGCCCCAACTCGTGTGTTACTGGAGTCTATACAGATCCATATCCCCTAATCTTCTATAGAAACCACACCTTGCGAGGGGTATTCGGGACAATGCTTGATGGTGTACAAGCAAGACTTAACCCTGCGTCTGCAGTATTCGATAGCACATCCCGCAGTCGCATTACTCGAGTGAGTTCAAGCAGTACCAAAGCAGCATACACAACATCAACTTGTTTTAAAGTGGTCAAGACTAATAAGACCTATTGTCTCAGCATTGCTGAAATATCTAATACTCTCTTCGGAGAATTCAGAATCGTCCCGTTACTAGTTGAGATCCTCAAAGATGACGGGGTTAGAGAAGCCAGGTCTGGCTAG SEQ ID NO:MDRAVSQVALENDEREAKNTWRLIFRIAILFLTVVTLAISVASLLYSMGASTPSDLVGIP34; NDV wildTRISRAEEKITSTLGSNQDVVDRIYKQVALESPLALLNTETTIMNAITSLSYQINGAANN type HNSGWGAPIHDPDYIGGIGKELIVDDASDVTSFYPSAFQEHLNFIPAPTTGSGCTRIPSFDM proteinSATHYCYTHNVILSGCRDHSHSYQYLALGVLRTSATGRVFFSTLRSINLDDTQNRKSCSV encoded bySATPLGCDMLCSKVTETEEEDYNSAVPTRMVHGRLGFDGQYHEKDLDVTTLFGDWVANYP SEQ ID NO:GVGGGSFIDSRVWFSVYGGLKPNSPSDTVQEGKYVIYKRYNDTCPDEQDYQIRMAKSSYK 33, fromPGRFGGKRIQQAILSIKVSTSLGEDPVLTVPPNTVTLMGAEGRILTVGTSHFLYQRGSSY accession #FSPALLYPMTVSNKTATLHSPYTFNAFTRPGSIPCQASARCPNSCVTGVYTDPYPLIFYR AF077761.1NHTLRGVFGTMLDGVQARLNPASAVFDSTSRSRITRVSSSSTKAAYTTSTCFKVVKTNKTYCLSIAEISNTLFGEFRIVPLLVEILKDDGVREARSG SEQ ID NO:GTGTCACCTTACATTCACATATCCAATGATTCTCAAAGGCTGTTCACTGAAGAAGGAGTC 35; encodesAAAGAGGGGAATGTGGTTTACCAACAGATC the stabilizing segment in L proteinSEQ ID NO: RRQRRF 36; mesogenic amino acid sequence SEQ ID NO:ACAGGTACGTTAATAGTTAATAGCGT 37; E_Sarbeco_ F1 SEQ ID NO:ATATTGCAGCAGTACGCACACA 38; E_Sarbeco_ R2 SEQ ID NO:FAM-ACACTAGCCATCCTTACTGCGCTTCG-BBQ 39; E_Sarbeco_ P1 SEQ ID NO:ATGTTCGTGTTCCTGGTCCTGCTGCCACTGGTAAGCTCCCAATGTGTAAACTTAACCACA 40AGAACCCAGCTCCCACCTGCCTACACCAACAGCTTCACCAGAGGCGTTTATTACCCCGAC chimericAAGGTATTCCGGTCTTCTGTTCTGCACTCTACCCAGGACCTGTTTCTGCCCTTTTTCAGC SARS-CoV-2AACGTGACATGGTTCCACGCCATCCACGTGTCTGGCACAAACGGCACCAAGCGGTTTGAT spike geneAATCCTGTGCTCCCTTTCAATGACGGCGTGTACTTCGCCTCTACTGAGAAGAGCAACATC encodingATCCGGGGCTGGATCTTTGGCACAACACTGGACTCTAAAACCCAGAGCCTGCTGATCGTG proteinAACAACGCCACCAACGTGGTGATTAAGGTGTGCGAGTTCCAGTTCTGCAATGACCCTTTC containingCTCGGCGTGTACTACCACAAGAACAACAAAAGTTGGATGGAAAGCGAATTCAGGGTGTAC theTCAAGCGCCAACAACTGTACCTTCGAGTACGTGAGCCAGCCTTTCCTGATGGACCTAGAAtransmembraneGGTAAGCAGGGCAATTTCAAGAACCTCAGAGAGTTCGTGTTCAAGAATATTGACGGCTAC (TM) andTTCAAAATCTACAGCAAGCACACCCCAATCAACCTGGTGCGGGACCTGCCCCAGGGCTTT cytoplasmicAGCGCGCTGGAGCCTCTGGTGGACCTGCCTATCGGCATCAACATCACCCGGTTCCAGACA (CT) domainCTGCTGGCTCTGCATAGAAGCTACCTGACACCTGGCGACAGTTCTTCTGGCTGGACAGCCof the NDV FGGCGCCGCCGCCTACTACGTGGGCTACCTGCAGCCTAGAACATTCCTGCTGAAATACAAC proteinGAGAACGGCACGATCACAGACGCCGTGGACTGCGCCCTGGATCCCCTGTCTGAGACAAAGTGCACCCTGAAGTCTTTCACCGTGGAGAAGGGCATCTACCAGACCTCCAACTTCAGAGTGCAGCCTACCGAATCCATCGTGCGCTTTCCCAACATCACCAACCTGTGCCCCTTCGGCGAGGTCTTTAATGCCACGAGATTCGCCAGCGTGTATGCCTGGAACAGAAAGAGAATCAGCAACTGCGTGGCCGACTACAGCGTGCTGTACAACAGCGCCTCTTTCAGCACATTTAAGTGCTACGGAGTGTCTCCTACCAAACTCAACGATCTGTGCTTCACGAACGTGTATGCCGACAGCTTCGTGATCCGAGGAGATGAGGTGCGGCAGATCGCTCCAGGACAGACAGGCAAGATCGCCGACTACAACTACAAGCTGCCCGACGACTTTACCGGCTGCGTGATCGCTTGGAACAGCAATAACCTGGACTCAAAGGTTGGAGGAAACTACAACTACCTGTACAGACTGTTCAGAAAGTCCAACCTGAAGCCCTTCGAGAGAGACATCTCTACAGAAATCTACCAGGCCGGCAGCACCCCATGTAACGGCGTGGAAGGCTTCAACTGCTACTTCCCTCTGCAGTCTTATGGCTTCCAGCCCACAAACGGAGTGGGCTATCAGCCTTACCGCGTGGTTGTCCTGAGCTTTGAGCTGCTGCATGCCCCTGCTACGGTGTGTGGACCTAAGAAGTCCACCAACCTGGTGAAGAACAAGTGTGTGAACTTCAACTTCAACGGCCTGACCGGCACCGGGGTGCTGACAGAGTCTAACAAGAAATTCCTGCCATTCCAGCAATTCGGCCGGGACATCGCCGACACCACCGACGCCGTGCGGGATCCTCAGACCCTCGAAATCCTGGACATCACCCCCTGTAGCTTCGGCGGCGTGAGCGTGATCACCCCTGGCACAAACACCAGCAATCAAGTGGCTGTCCTGTACCAGGATGTCAATTGCACAGAAGTGCCTGTGGCCATCCACGCCGATCAGCTGACCCCCACCTGGCGGGTGTACTCGACAGGAAGCAACGTGTTTCAAACAAGAGCCGGCTGCCTGATCGGGGCCGAGCACGTGAACAATTCCTACGAGTGCGACATCCCCATCGGCGCCGGCATCTGTGCCTCTTACCAGACACAGACCAATTCCCCTggtagtgcaagtTCCGTGGCCAGCCAGAGCATCATCGCCTACACCATGAGCCTGGGCGCCGAAAACAGCGTTGCATATTCCAACAACAGCATCGCCATCCCTACCAACTTCACCATCAGCGTGACCACAGAAATCCTGCCTGTGTCCATGACCAAGACAAGCGTTGATTGCACCATGTACATCTGCGGCGATAGCACAGAGTGCAGCAATCTGCTGCTGCAGTACGGTAGCTTCTGCACCCAGCTGAATAGAGCCCTGACCGGCATCGCTGTGGAACAGGACAAAAACACCCAGGAGGTCTTCGCCCAGGTGAAGCAAATCTACAAGACCCCTCCAATCAAGGACTTCGGAGGCTTTAACTTTAGCCAGATCCTGCCTGATCCCTCCAAGCCTAGCAAACGGAGTcctATCGAGGACCTGCTCTTCAACAAGGTGACCCTGGCTGACGCCGGCTTCATTAAGCAGTACGGCGATTGCCTCGGCGACATCGCTGCAAGAGACCTGATCTGCGCCCAGAAGTTCAACGGCCTGACCGTGCTGCCTCCTCTCCTGACAGACGAGATGATCGCCCAGTACACCTCTGCCCTTCTGGCTGGCACCATCACCAGCGGATGGACCTTTGGAGCCGGAcctGCCCTGCAGATCCCTTTCcctATGCAGATGGCCTACAGATTCAACGGGATCGGAGTGACCCAAAACGTGCTGTATGAAAACCAGAAACTGATCGCCAATCAGTTTAACAGCGCCATCGGCAAAATCCAGGATAGCCTGTCCAGCACCccaAGCGCCCTCGGCAAGCTGCAAGATGTGGTGAATCAAAATGCCCAAGCCCTGAACACACTGGTGAAGCAGCTGAGCAGCAACTTCGGCGCCATCAGCAGCGTGCTGAACGACATCCTGAGCAGACTGGACccacctGAAGCCGAGGTGCAGATCGACAGACTGATCACAGGCAGACTGCAGTCCCTGCAGACCTACGTGACCCAGCAGTTGATTAGAGCCGCTGAGATTAGAGCCAGTGCCAACCTGGCTGCCACAAAGATGTCAGAATGCGTGCTGGGCCAGAGCAAGAGAGTGGACTTCTGCGGCAAAGGCTACCACCTGATGAGCTTTCCTCAGTCTGCACCCCACGGCGTGGTGTTTCTCCACGTGACATACGTGCCCGCGCAAGAAAAGAACTTTACAACCGCCCCAGCGATCTGCCACGACGGCAAGGCCCACTTCCCTCGGGAGGGTGTGTTCGTGAGCAATGGAACACACTGGTTCGTCACCCAGCGGAACTTCTACGAGCCTCAGATCATTACCACCGACAACACCTTCGTGAGCGGCAACTGTGACGTCGTTATCGGCATCGTGAACAATACCGTGTACGACCCCCTGCAGCCTGAGCTGGATAGCTTCAAAGAGGAACTGGACAAGTACTTCAAGAACCACACAAGCCCCGACGTGGACCTAGGCGACATCTCTGGAATCAACGCCAGCGTGGTGAACATCCAAAAGGAAATCGACAGACTGAACGAGGTGGCCAAGAATCTGAATGAAAGCCTGATCGATCTGCAGGAGCTGGGCAAGTACGAGCAGggtggcggtggctcgCTGATTACCTATATCGTCCTGACTATTATCTCCCTGGTGTTTGGCATTCTGTCCCTGATTCTGGCCTGTTACCTGATGTACAAGCAGAAGGCCCAGCAGAAGACCCTGCTGTGGCTGGGCAATAATACACTGGATCAGATGCGGGCTACAACTAAGATGTGA SEQ ID NO:MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS 41NVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIV chimericNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLE SARS-CoV-2GKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTspike proteinLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETK containingCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISN theCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADtransmembraneYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPC (TM) andNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVN cytoplasmicFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITP (CT) domainGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYof the NDV FECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTI proteinSVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGPALQIPFPMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQGGGGSLITYIVLTIISLVFGILSLILACYLMYKQKAQQKTLLWLGNNTLDQM RATTKMSEQ ID NO: TAATACGACTCACTATAGGGACCAAACAGAGAATCCGTGAGTTACGATAAAAGGCGAAGG42 AGCAATTGAAGTCGCACGGGTAGAAGGTGTGAATCTCGAGTGCGAGCCCGAAGCACAAAC NDV-TCGAGAAAGCCTTCTGCCAACATGTCTTCCGTATTTGATGAGTACGAACAGCTCCTCGCG MolecularGCTCAGACTCGCCCCAATGGAGCTCATGGAGGGGGAGAAAAAGGGAGTACCTTAAAAGTA CloneGACGTCCCGGTATTCACTCTTAACAGTGATGACCCAGAAGATAGATGGAGCTTTGTGGTA AF077761.1_TTCTGCCTCCGGATTGCTGTTAGCGAAGATGCCAACAAACCACTCAGGCAAGGTGCTCTC LaSota_KanATATCTCTTTTATGCTCCCACTCACAGGTAATGAGGAACCATGTTGCCATTGCAGGGAAA R (withCAGAATGAAGCCACATTGGCCGTGCTTGAGATTGATGGCTTTGCCAACGGCACGCCCCAG stabilizingTTCAACAATAGGAGTGGAGTGTCTGAAGAGAGAGCACAGAGATTTGCGATGATAGCAGGA sequence inTCTCTCCCTCGGGCATGCAGCAACGGAACCCCGTTCGTCACAGCCGGGGCAGAAGATGAT L) backboneGCACCAGAAGACATCACCGATACCCTGGAGAGGATCCTCTCTATCCAGGCTCAAGTATGGGTCACAGTAGCAAAAGCCATGACTGCGTATGAGACTGCAGATGAGTCGGAAACAAGGCGAATCAATAAGTATATGCAGCAAGGCAGGGTCCAAAAGAAATACATCCTCTACCCCGTATGCAGGAGCACAATCCAACTCACGATCAGACAGTCTCTTGCAGTCCGCATCTTTTTGGTTAGCGAGCTCAAGAGAGGCCGCAACACGGCAGGTGGTACCTCTACTTATTATAACCTGGTAGGGGACGTAGACTCATACATCAGGAATACCGGGCTTACTGCATTCTTCTTGACACTCAAGTACGGAATCAACACCAAGACATCAGCCCTTGCACTTAGTAGCCTCTCAGGCGACATCCAGAAGATGAAGCAGCTCATGCGTTTGTATCGGATGAAAGGAGATAATGCGCCGTACATGACATTACTTGGTGATAGTGACCAGATGAGCTTTGCGCCTGCCGAGTATGCACAACTTTACTCCTTTGCCATGGGTATGGCATCAGTCCTAGATAAAGGTACTGGGAAATACCAATTTGCCAGGGACTTTATGAGCACATCATTCTGGAGACTTGGAGTAGAGTACGCTCAGGCTCAGGGAAGTAGCATTAACGAGGATATGGCTGCCGAGCTAAAGCTAACCCCAGCAGCAATGAAGGGCCTGGCAGCTGCTGCCCAACGGGTCTCCGACGATACCAGCAGCATATACATGCCTACTCAACAAGTCGGAGTCCTCACTGGGCTTAGCGAGGGGGGGTCCCAAGCTCTACAAGGCGGATCGAATAGATCGCAAGGGCAACCAGAAGCCGGGGATGGGGAGACCCAATTCCTGGATCTGATGAGAGCGGTAGCAAATAGCATGAGGGAGGCGCCAAACTCTGCACAGGGCACTCCCCAATCGGGGCCTCCCCCAACTCCTGGGCCATCCCAAGATAACGACACCGACTGGGGGTATTGATGGACAAAACCCAGCCTGCTTCCACAAAAACATCCCAATGCCCTCACCCGTAGTCGACCCCTCGATTTGCGGCTCTATATGACCACACCCTCAAACAAACATCCCCCTCTTTCCTCCCTCCCCCTGCTGTACAACTCCGCACGCCCTAGATACCACAGGCACAATGCGGCTCACTAACAATCAAAACAGAGCCGAGGGAATTAGAAAAAAGTACGGGTAGAAGAGGGATATTCAGAGATCAGGGCAAGTCTCCCGAGTCTCTGCTCTCTCCTCTACCTGATAGACCAGGACAAACATGGCCACCTTTACAGATGCAGAGATCGACGAGCTATTTGAGACAAGTGGAACTGTCATTGACAACATAATTACAGCCCAGGGTAAACCAGCAGAGACTGTTGGAAGGAGTGCAATCCCACAAGGCAAGACCAAGGTGCTGAGCGCAGCATGGGAGAAGCATGGGAGCATCCAGCCACCGGCCAGTCAAGACAACCCCGATCGACAGGACAGATCTGACAAACAACCATCCACACCCGAGCAAACGACCCCGCATGACAGCCCGCCGGCCACATCCGCCGACCAGCCCCCCACCCAGGCCACAGACGAAGCCGTCGACACACAGTTCAGGACCGGAGCAAGCAACTCTCTGCTGTTGATGCTTGACAAGCTCAGCAATAAATCGTCCAATGCTAAAAAGGGCCCATGGTCGAGCCCCCAAGAGGGGAATCACCAACGTCCGACTCAACAGCAGGGGAGTCAACCCAGTCGCGGAAACAGTCAGGAAAGACCGCAGAACCAAGTCAAGGCCGCCCCTGGAAACCAGGGCACAGACGTGAACACAGCATATCATGGACAATGGGAGGAGTCACAACTATCAGCTGGTGCAACCCCTCATGCTCTCCGATCAAGGCAGAGCCAAGACAATACCCTTGTATCTGCGGATCATGTCCAGCCACCTGTAGACTTTGTGCAAGCGATGATGTCTATGATGGAGGCGATATCACAGAGAGTAAGTAAGGTTGACTATCAGCTAGATCTTGTCTTGAAACAGACATCCTCCATCCCTATGATGCGGTCCGAAATCCAACAGCTGAAAACATCTGTTGCAGTCATGGAAGCCAACTTGGGAATGATGAAGATTCTGGATCCCGGTTGTGCCAACATTTCATCTCTGAGTGATCTACGGGCAGTTGCCCGATCTCACCCGGTTTTAGTTTCAGGCCCTGGAGACCCCTCTCCCTATGTGACACAAGGAGGCGAAATGGCACTTAATAAACTTTCGCAACCAGTGCCACATCCATCTGAATTGATTAAACCCGCCACTGCATGCGGGCCTGATATAGGAGTGGAAAAGGACACTGTCCGTGCATTGATCATGTCACGCCCAATGCACCCGAGTTCTTCAGCCAAGCTCCTAAGCAAGTTAGATGCAGCCGGGTCGATCGAGGAAATCAGGAAAATCAAGCGCCTTGCTCTAAATGGCTAATTACTACTGCCACACGTAGCGGGTCCCTGTCCACTCGGCATCACACGGAATCTGCACCGAGTTCCCCCtctagaTTAGAAAAAATACGGGTAGAACCGCCACCacgcgtACCCAAGGTCCAACTCTCCAAGCGGCAATCCTCTCTCGCTTCCTCAGCCCCACTGAATGGTCGCGTAACCGTAATTAATCTAGCTACATTTAAGATTAAGAAAAAATACGGGTAGAATTGGAGTGCCCCAATTGTGCCAAGATGGACTCATCTAGGACAATTGGGCTGTACTTTGATTCTGCCCATTCTTCTAGCAACCTGTTAGCATTTCCGATCGTCCTACAAGGCACAGGAGATGGGAAGAAGCAAATCGCCCCGCAATATAGGATCCAGCGCCTTGACTTGTGGACTGATAGTAAGGAGGACTCAGTATTCATCACCACCTATGGATTCATCTTTCAAGTTGGGAATGAAGAAGCCACTGTCGGCATGATCGATGATAAACCCAAGCGCGAGTTACTTTCCGCTGCGATGCTCTGCCTAGGAAGCGTCCCAAATACCGGAGACCTTATTGAGCTGGCAAGGGCCTGTCTCACTATGATAGTCACATGCAAGAAGAGTGCAACTAATACTGAGAGAATGGTTTTCTCAGTAGTGCAGGCACCCCAAGTGCTGCAAAGCTGTAGGGTTGTGGCAAACAAATACTCATCAGTGAATGCAGTCAAGCACGTGAAAGCGCCAGAGAAGATTCCCGGGAGTGGAACCCTAGAATACAAGGTGAACTTTGTCTCCTTGACTGTGGTACCGAAGAAGGATGTCTACAAGATCCCAGCTGCAGTATTGAAGGTTTCTGGCTCGAGTCTGTACAATCTTGCGCTCAATGTCACTATTAATGTGGAGGTAGACCCGAGGAGTCCTTTGGTTAAATCTTTGTCTAAGTCTGACAGCGGATACTATGCTAACCTCTTCTTGCATATTGGACTTATGACCACCGTAGATAGGAAGGGGAAGAAAGTGACATTTGACAAGCTGGAAAAGAAAATAAGGAGCCTTGATCTATCTGTCGGGCTCAGTGATGTGCTCGGGCCTTCCGTGTTGGTAAAAGCAAGAGGTGCACGGACTAAGCTTTTGGCACCTTTCTTCTCTAGCAGTGGGACAGCCTGCTATCCCATAGCAAATGCTTCTCCTCAGGTGGCCAAGATACTCTGGAGTCAAACCGCGTGCCTGCGGAGCGTTAAAATCATTATCCAAGCAGGTACCCAACGCGCTGTCGCAGTGACCGCCGACCACGAGGTTACCTCTACTAAGCTGGAGAAGGGGCACACCCTTGCCAAATACAATCCTTTTAAGAAATAAGCTGCGTCTCTGAGATTGCGCTCCGCCCACTCACCCAGATCATCATGACACAAAAAACTAATCTGTCTTGATTATTTACAGTTAGTTTACCTGTCTATCAAGTTAGAAAAAACACGGGTAGAAGATTCTGGATCCCGGTTGGCGCCCTCCAGGTGCAAGttaattaaATGGGCTCCAGACCTTCTACCAAGAACCCAGCACCTATGATGCTGACTATCCGGGTTGCGCTGGTACTGAGTTGCATCTGTCCGGCAAACTCCATTGATGGCAGGCCTCTTGCAGCTGCAGGAATTGTGGTTACAGGAGACAAAGCCGTCAACATATACACCTCATCCCAGACAGGATCAATCATAGTTAAGCTCCTCCCGAATCTGCCCAAGGATAAGGAGGCATGTGCGAAAGCCCCCTTGGATGCATACAACAGGACATTGACCACTTTGCTCACCCCCCTTGGTGACTCTATCCGTAGGATACAAGAGTCTGTGACTACATCTGGAGGGGGGAGACAGGGGCGCCTTATAGGCGCCATTATTGGCGGTGTGGCTCTTGGGGTTGCAACTGCCGCACAAATAACAGCGGCCGCAGCTCTGATACAAGCCAAACAAAATGCTGCCAACATCCTCCGACTTAAAGAGAGCATTGCCGCAACCAATGAGGCTGTGCATGAGGTCACTGACGGATTATCGCAACTAGCAGTGGCAGTTGGGAAGATGCAGCAGTTTGTTAATGACCAATTTAATAAAACAGCTCAGGAATTAGACTGCATCAAAATTGCACAGCAAGTTGGTGTAGAGCTCAACCTGTACCTAACCGAATTGACTACAGTATTCGGACCACAAATCACTTCACCTGCTTTAAACAAGCTGACTATTCAGGCACTTTACAATCTAGCTGGTGGAAATATGGATTACTTATTGACTAAGTTAGGTGTAGGGAACAATCAACTCAGCTCATTAATCGGTAGCGGCTTAATCACtGGcAACCCTATTCTATACGACTCACAGACTCAACTCTTGGGTATACAGGTAACTgcaCCTTCAGTCGGGAACCTAAATAATATGCGTGCCACCTACTTGGAAACCTTATCCGTAAGCACAACCAGGGGATTTGCCTCGGCACTTGTCCCCAAAGTGGTGACACAGGTCGGTTCTGTGATAGAAGAACTTGACACCTCATACTGTATAGAAACTGACTTAGATTTATATTGTACAAGAATAGTAACGTTCCCTATGTCCCCTGGTATTTATTCCTGCTTGAGCGGCAATACGTCGGCCTGTATGTACTCAAAGACCGAAGGCGCACTTACTACACCATACATGACTATCAAAGGTTCAGTCATCGCCAACTGCAAGATGACAACATGTAGATGTGTAAACCCCCCGGGTATCATATCGCAAAACTATGGAGAAGCCGTGTCTCTAATAGATAAACAATCATGCAATGTTTTATCCTTAGGCGGGATAACTTTAAGGCTCAGTGGGGAATTCGATGTAACTTATCAGAAGAATATCTCAATACAAGATTCTCAAGTAATAATAACAGGCAATCTTGATATCTCAACTGAGCTTGGGAATGTCAACAACTCGATCAGTAATGCTTTGAATAAGTTAGAGGAAAGCAACAGAAAACTAGACAAAGTCAATGTCAAACTGACTAGCACATCTGCTCTCATTACgTATATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTGATTCTAGCATGCTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTTATTATGGCTTGGGAATAATACaCTcGATCAGATGAGAGCCACTACAAAAATGTGAACACAGATGAGGAACGAAGGTTTCCCTAATAGTAATTTGTGTGAAAGTTCTGGTAGTCTGTCAGTTCAGAGAGTTAAGAAAAAACTACCGGTTGTAGATGACCAAAGGACGATATACGGGTAGAACGGTAAGAGAGGCCGCCCCTCAATTGCGAGCCAGGCTTCACAACCTCCGTTCTACCGCTTCACCGACAACAGTCCTCAATCATGGACCGCGCCGTTAGCCAAGTTGCGTTAGAGAATGATGAAAGAGAGGCAAAAAATACATGGCGCTTGATATTCCGGATTGCAATCTTATTCTTAACAGTAGTGACCTTGGCTATATCTGTAGCCTCCCTTTTATATAGCATGGGGGCTAGCACACCTAGCGATCTTGTAGGCATACCGACTAGGATTTCCAGGGCAGAAGAAAAGATTACATCTACACTTGGTTCCAATCAAGATGTAGTAGATAGGATATATAAGCAAGTGGCCCTTGAGTCTCCGTTGGCATTGTTAAATACTGAGACCACAATTATGAACGCAATAACATCTCTCTCTTATCAGATTAATGGAGCTGCAAACAACAGTGGGTGGGGGGCACCTATCCATGACCCAGATTATATAGGGGGGATAGGCAAAGAACTCATTGTAGATGATGCTAGTGATGTCACATCATTCTATCCCTCTGCATTTCAAGAACATCTGAATTTTATCCCGGCGCCTACTACAGGATCAGGTTGCACTCGAATACCCTCATTTGACATGAGTGCTACCCATTACTGCTACACCCATAATGTAATATTGTCTGGATGCAGAGATCACTCACATTCATATCAGTATTTAGCACTTGGTGTGCTCCGGACATCTGCAACAGGGAGGGTATTCTTTTCTACTCTGCGTTCCATCAACCTGGACGACACCCAAAATCGGAAGTCTTGCAGTGTGAGTGCAACTCCCCTGGGTTGTGATATGCTGTGCTCGAAAGTCACGGAGACAGAGGAAGAAGATTATAACTCAGCTGTCCCTACGCGGATGGTACATGGGAGGTTAGGGTTCGACGGCCAGTACCACGAAAAGGACCTAGATGTCACAACATTATTCGGGGACTGGGTGGCCAACTACCCAGGAGTAGGGGGTGGATCTTTTATTGACAGCCGCGTATGGTTCTCAGTCTACGGAGGGTTAAAACCCAATTCACCCAGTGACACTGTACAGGAAGGGAAATATGTGATATACAAGCGATACAATGACACATGCCCAGATGAGCAAGACTACCAGATTCGAATGGCCAAGTCTTCGTATAAGCCTGGACGGTTTGGTGGGAAACGCATACAGCAGGCTATCTTATCTATCAAGGTGTCAACATCCTTAGGCGAAGACCCGGTACTGACTGTACCGCCCAACACAGTCACACTCATGGGGGCCGAAGGCAGAATTCTCACAGTAGGGACATCTCATTTCTTGTATCAACGAGGGTCATCATACTTCTCTCCCGCGTTATTATATCCTATGACAGTCAGCAACAAAACAGCCACTCTTCATAGTCCTTATACATTCAATGCCTTCACTCGGCCAGGTAGTATCCCTTGCCAGGCTTCAGCAAGATGCCCCAACTCGTGTGTTACTGGAGTCTATACAGATCCATATCCCCTAATCTTCTATAGAAACCACACCTTGCGAGGGGTATTCGGGACAATGCTTGATGGTGTACAAGCAAGACTTAACCCTGCGTCTGCAGTATTCGATAGCACATCCCGCAGTCGCATTACTCGAGTGAGTTCAAGCAGTACCAAAGCAGCATACACAACATCAACTTGTTTTAAAGTGGTCAAGACTAATAAGACCTATTGTCTCAGCATTGCTGAAATATCTAATACTCTCTTCGGAGAATTCAGAATCGTCCCGTTACTAGTTGAGATCCTCAAAGATGACGGGGTTAGAGAAGCCAGGTCTGGCTAGggcgcgccTTGAGTCAATTATAAAGGAGTTGGAAAGATGGCATTGTATCACCTATCTTCTGCGACATCAAGAATCAAACCGAATGCCGGCGCGTGCTCGAATTCCATGTTGCCAGTTGACCACAATCAGCCAGTGCTCATGCGATCAGATTAAGCCTTGTCATTAATCTCTTGATTAAGAAAAAATGTAAGTGGCAATGAGATACAAGGCAAAACAGCTCATGGTAAATAATACGGGTAGGACATGGCGAGCTCCGGTCCTGAAAGGGCAGAGCATCAGATTATCCTACCAGAGCCACACCTGTCTTCACCATTGGTCAAGCACAAACTACTCTATTACTGGAAATTAACTGGGCTACCGCTTCCTGATGAATGTGACTTCGACCACCTCATTCTCAGCCGACAATGGAAAAAAATACTTGAATCGGCCTCTCCTGATACTGAGAGAATGATAAAACTCGGAAGGGCAGTACACCAAACTCTTAACCACAATTCCAGAATAACCGGAGTGCTCCACCCCAGGTGTTTAGAACAACTGGCTAATATTGAGGTCCCAGATTCAACCAACAAATTTCGGAAGATTGAGAAGAAGATCCAAATTCACAACACGAGATATGGAGAACTGTTCACAAGGCTGTGTACGCATATAGAGAAGAAACTGCTGGGGTCATCTTGGTCTAACAATGTCCCCCGGTCAGAGGAGTTCAGCAGCATTCGTACGGATCCGGCATTCTGGTTTCACTCAAAATGGTCCACAGCCAAGTTTGCATGGCTCCATATAAAACAGATCCAGAGGCATCTGATGGTGGCAGCTAAGACAAGGTCTGCGGCCAACAAATTGGTGATGCTAACCCATAAGGTAGGCCAAGTCTTTGTCACTCCTGAACTTGTCGTTGTGACGCATACGAATGAGAACAAGTTCACATGTCTTACCCAGGAACTTGTATTGATGTATGCAGATATGATGGAGGGCAGAGATATGGTCAACATAATATCAACCACGGCGGTGCATCTCAGAAGCTTATCAGAGAAAATTGATGACATTTTGCGGTTAATAGACGCTCTGGCAAAAGACTTGGGTAATCAAGTCTACGATGTTGTATCACTAATGGAGGGATTTGCATACGGAGCTGTCCAGCTACTCGAGCCGTCAGGTACATTTGCAGGAGATTTCTTCGCATTCAACCTGCAGGAGCTTAAAGACATTCTAATTGGCCTCCTCCCCAATGATATAGCAGAATCCGTGACTCATGCAATCGCTACTGTATTCTCTGGTTTAGAACAGAATCAAGCAGCTGAGATGTTGTGTCTGTTGCGTCTGTGGGGTCACCCACTGCTTGAGTCCCGTATTGCAGCAAAGGCAGTCAGGAGCCAAATGTGCGCACCGAAAATGGTAGACTTTGATATGATCCTTCAGGTACTGTCTTTCTTCAAGGGAACAATCATCAACGGGTACAGAAAGAAGAATGCAGGTGTGTGGCCGCGAGTCAAAGTGGATACAATATATGGGAAGGTCATTGGGCAACTACATGCAGATTCAGCAGAGATTTCACACGATATCATGTTGAGAGAGTATAAGAGTTTATCTGCACTTGAATTTGAGCCATGTATAGAATATGACCCTGTCACCAACCTGAGCATGTTCCTAAAAGACAAGGCAATCGCACACCCCAACGATAATTGGCTTGCCTCGTTTAGGCGGAACCTTCTCTCCGAAGACCAGAAGAAACATGTAAAAGAAGCAACTTCGACTAATCGCCTCTTGATAGAGTTTTTAGAGTCAAATGATTTTGATCCATATAAAGAGATGGAATATCTGACGACCCTTGAGTACCTTAGAGATGACAATGTGGCAGTATCATACTCGCTCAAGGAGAAGGAAGTGAAAGTTAATGGACGGATCTTCGCTAAGCTGACAAAGAAGTTAAGGAACTGTCAGGTGATGGCGGAAGGGATCCTAGCCGATCAGATTGCACCTTTCTTTCAGGGAAATGGAGTCATTCAGGATAGCATATCCTTGACCAAGAGTATGCTAGCGATGAGTCAACTGTCTTTTAACAGCAATAAGAAACGTATCACTGACTGTAAAGAAAGAGTATCTTCAAACCGCAATCATGATCCGAAAAGCAAGAACCGTCGGAGAGTTGCAACCTTCATAACAACTGACCTGCAAAAGTACTGTCTTAATTGGAGATATCAGACAATCAAATTGTTCGCTCATGCCATCAATCAGTTGATGGGCCTACCTCACTTCTTCGAATGGATTCACCTAAGACTGATGGACACTACGATGTTCGTAGGAGACCCTTTCAATCCTCCAAGTGACCCTACTGACTGTGACCTCTCAAGAGTCCCTAATGATGACATATATATTGTCAGTGCCAGAGGGGGTATCGAAGGATTATGCCAGAAGCTATGGACAATGATCTCAATTGCTGCAATCCAACTTGCTGCAGCTAGATCGCATTGTCGTGTTGCCTGTATGGTACAGGGTGATAATCAAGTAATAGCAGTAACGAGAGAGGTAAGATCAGACGACTCTCCGGAGATGGTGTTGACACAGTTGCATCAAGCCAGTGATAATTTCTTCAAGGAATTAATTCATGTCAATCATTTGATTGGCCATAATTTGAAGGATCGTGAAACCATCAGGTCAGACACATTCTTCATATACAGCAAACGAATCTTCAAAGATGGAGCAATCCTCAGTCAAGTCCTCAAAAATTCATCTAAATTAGTGCTAGTGTCAGGTGATCTCAGTGAAAACACCGTAATGTCCTGTGCCAACATTGCCTCTACTGTAGCACGGCTATGCGAGAACGGGCTTCCCAAAGACTTCTGTTACTATTTAAACTATATAATGAGTTGTGTGCAGACATACTTTGACTCTGAGTTCTCCATCACCAACAATTCGCACCCCGATCTTAATCAGTCGTGGATTGAGGACATCTCTTTTGTGCACTCATATGTTCTGACTCCTGCCCAATTAGGGGGACTGAGTAACCTTCAATACTCAAGGCTCTACACTAGAAATATCGGTGACCCGGGGACTACTGCTTTTGCAGAGATCAAGCGACTAGAAGCAGTGGGATTACTGAGTCCTAACATTATGACTAATATCTTAACTAGGCCGCCTGGGAATGGAGATTGGGCCAGTCTGTGCAACGACCCATACTCTTTCAATTTTGAGACTGTTGCAAGCCCAAATATTGTTCTTAAGAAACATACGCAAAGAGTCCTATTTGAAACTTGTTCAAATCCCTTATTGTCTGGAGTGCACACAGAGGATAATGAGGCAGAAGAGAAGGCATTGGCTGAATTCTTGCTTAATCAAGAGGTGATTCATCCCCGCGTTGCGCATGCCATCATGGAGGCAAGCTCTGTAGGTAGGAGAAAGCAAATTCAAGGGCTTGTTGACACAACAAACACCGTAATTAAGATTGCGCTTACTAGGAGGCCATTAGGCATCAAGAGGCTGATGCGGATAGTCAATTATTCTAGCATGCATGCAATGCTGTTTAGAGACGATGTTTTTTCCTCCAGTAGATCCAACCACCCCTTAGTCTCTTCTAATATGTGTTCTCTGACACTGGCAGACTATGCACGGAATAGAAGCTGGTCACCTTTGACGGGAGGCAGGAAAATACTGGGTGTATCTAATCCTGATACGATAGAACTCGTAGAGGGTGAGATTCTTAGTGTAAGCGGAGGGTGTACAAGATGTGACAGCGGAGATGAACAATTTACTTGGTTCCATCTTCCAAGCAATATAGAATTGACCGATGACACCAGCAAGAATCCTCCGATGAGGGTACCATATCTCGGGTCAAAGACACAGGAGAGGAGAGCTGCCTCACTTGCAAAAATAGCTCATATGTCGCCACATGTAAAGGCTGCCCTAAGGGCATCATCCGTGTTGATCTGGGCTTATGGGGATAATGAAGTAAATTGGACTGCTGCTCTTACGATTGCAAAATCTCGGTGTAATGTAAACTTAGAGTATCTTCGGTTACTGTCCCCTTTACCCACGGCTGGGAATCTTCAACATAGACTAGATGATGGTATAACTCAGATGACATTCACCCCTGCATCTCTCTACAGGgtgtcaccttacattcacatatccaatgattctcaaaggctgttcactgaagaaggagtcaaagaggggaatgtggtttaccaacagatcATGCTCTTGGGTTTATCTCTAATCGAATCGATCTTTCCAATGACAACAACCAGGACATATGATGAGATCACACTGCACCTACATAGTAAATTTAGTTGCTGTATCAGAGAAGCACCTGTTGCGGTTCCTTTCGAGCTACTTGGGGTGGTACCGGAACTGAGGACAGTGACCTCAAATAAGTTTATGTATGATCCTAGCCCTGTATCGGAGGGAGACTTTGCGAGACTTGACTTAGCTATCTTCAAGAGTTATGAGCTTAATCTGGAGTCATATCCCACGATAGAGCTAATGAACATTCTTTCAATATCCAGCGGGAAGTTGATTGGCCAGTCTGTGGTTTCTTATGATGAAGATACCTCCATAAAGAATGACGCCATAATAGTGTATGACAATACCCGAAATTGGATCAGTGAAGCTCAGAATTCAGATGTGGTCCGCCTATTTGAATATGCAGCACTTGAAGTGCTCCTCGACTGTTCTTACCAACTCTATTACCTGAGAGTAAGAGGCCTAGACAATATTGTCTTATATATGGGTGATTTATACAAGAATATGCCAGGAATTCTACTTTCCAACATTGCAGCTACAATATCTCATCCCGTCATTCATTCAAGGTTACATGCAGTGGGCCTGGTCAACCATGACGGATCACACCAACTTGCAGATACGGATTTTATCGAAATGTCTGCAAAACTATTAGTATCTTGCACCCGACGTGTGATCTCCGGCTTATATTCAGGAAATAAGTATGATCTGCTGTTCCCATCTGTCTTAGATGATAACCTGAATGAGAAGATGCTTCAGCTGATATCCCGGTTATGCTGTCTGTACACGGTACTCTTTGCTACAACAAGAGAAATCCCGAAAATAAGAGGCTTAACTGCAGAAGAGAAATGTTCAATACTCACTGAGTATTTACTGTCGGATGCTGTGAAACCATTACTTAGCCCCGATCAAGTGAGCTCTATCATGTCTCCTAACATAATTACATTCCCAGCTAATCTGTACTACATGTCTCGGAAGAGCCTCAATTTGATCAGGGAAAGGGAGGACAGGGATACTATCCTGGCGTTGTTGTTCCCCCAAGAGCCATTATTAGAGTTCCCTTCTGTGCAAGATATTGGTGCTCGAGTGAAAGATCCATTCACCCGACAACCTGCGGCATTTTTGCAAGAGTTAGATTTGAGTGCTCCAGCAAGGTATGACGCATTCACACTTAGTCAGATTCATCCTGAACTCACATCTCCAAATCCGGAGGAAGACTACTTAGTACGATACTTGTTCAGAGGGATAGGGACTGCATCTTCCTCTTGGTATAAGGCATCTCATCTCCTTTCTGTACCCGAGGTAAGATGTGCAAGACACGGGAACTCCTTATACTTAGCTGAAGGGAGCGGAGCCATCATGAGTCTTCTCGAACTGCATGTACCACATGAAACTATCTATTACAATACGCTCTTTTCAAATGAGATGAACCCCCCGCAACGACATTTCGGGCCGACCCCAACTCAGTTTTTGAATTCGGTTGTTTATAGGAATCTACAGGCGGAGGTAACATGCAAAGATGGATTTGTCCAAGAGTTCCGTCCATTATGGAGAGAAAATACAGAGGAAAGTGACCTGACCTCAGATAAAGCAGTGGGGTATATTACATCTGCAGTGCCCTACAGATCTGTATCATTGCTGCATTGTGACATTGAAATTCCTCCAGGGTCCAATCAAAGCTTACTAGATCAACTAGCTATCAATTTATCTCTGATTGCCATGCATTCTGTAAGGGAGGGCGGGGTAGTAATCATCAAAGTGTTGTATGCAATGGGATACTACTTTCATCTACTCATGAACTTGTTTGCTCCGTGTTCCACAAAAGGATATATTCTCTCTAATGGTTATGCATGTCGAGGAGATATGGAGTGTTACCTGGTATTTGTCATGGGTTACCTGGGCGGGCCTACATTTGTACATGAGGTGGTGAGGATGGCAAAAACTCTGGTGCAGCGGCACGGTACGCTCTTGTCTAAATCAGATGAGATCACACTGACCAGGTTATTCACCTCACAGCGGCAGCGTGTGACAGACATCCTATCCAGTCCTTTACCAAGATTAATAAAGTACTTGAGGAAGAATATTGACACTGCGCTGATTGAAGCCGGGGGACAGCCCGTCCGTCCATTCTGTGCGGAGAGTCTGGTGAGCACGCTAGCGAACATAACTCAGATAACCCAGATTATCGCTAGTCACATTGACACAGTTATCCGGTCTGTGATATATATGGAAGCTGAGGGTGATCTCGCTGACACAGTATTTCTATTTACCCCTTACAATCTCTCTACTGACGGGAAAAAGAGGACATCACTTATACAGTGCACGAGACAGATCCTAGAGGTTACAATACTAGGTCTTAGAGTCGAAAATCTCAATAAAATAGGCGATATAATCAGCCTAGTGCTTAAAGGCATGATCTCCATGGAGGACCTTATCCCACTAAGGACATACTTGAAGCATAGTACCTGCCCTAAATATTTGAAGGCTGTCCTAGGTATTACCAAACTCAAAGAAATGTTTACAGACACTTCTGTATTGTACTTGACTCGTGCTCAACAAAAATTCTACATGAAAACTATAGGCAATGCAGTCAAAGGATATTACAGTAACTGTGAGTCTTAACGAAAATCACATATTAATAGGCTCCTTTTTTGGCCAATTGTATTCTTGTTGATTTAATCATATTATGTTAGAAAAAAGTTGAACCCTGACTCCTTAGGACTCGAATTCGAACTCAAATAAATGTCTTAAAAAAAGGTTGCGCACAATTATTCTTGAGTGTAGTCTCGTCATTCACCAAATCTTTGTTTGGTGGCCGGCATGGTCCCAGCCTCCTCGCTGGCGCCGGCTGGGCAACATTCCGAGGGGACCGTCCCCTCGGTAATGGCGAATGGGACGTCGACTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTATA

Inventors have also engineered and rescued a chimeric NDV virus that hasthe F protein and HN protein from avian paramyxovirus 5 (APMV5) (SEQ IDNO: 9). F protein and HN protein are constituents of the NDV envelope,embedded within the lipid bilayer membrane. The inventors designed andproduced this chimeric virus because the APMV5 F gene has a multi-basiccleavage site, which, without wishing to be bound by theory, can beuseful for fusion with cells. Since APMV-5 is not pathogenic inchickens, the swapping of portion of APMV5 F protein with NDV F proteinwould broaden the use of this virus as an oncolytic agent injurisdictions where there are restrictions imposed on avian pathogens,for example in the US by the authority of USDA/CDC. Specifically, forthe NDV-APMV5 F-HN chimeric molecular clone sequence, NDV-APMV5 F iscomposed mostly of APMV5 but the last 53 amino acids are from NDV.NDV-APMV5 HN is composed mostly of APMV5 but the first 53 amino acidsare from NDV.

Accordingly, also provided is an engineered NDV vector comprising anucleic acid having a nucleic acid sequence encoding a L proteincomprising a stabilizing segment, a chimeric F protein, and a chimericHN protein, wherein the chimeric F protein comprises avian paramyxovirus5 (APMV5) F protein segment thereof at the N-terminus and an NDV Fprotein segment at the C-terminus, and wherein the chimeric HN proteincomprises an NDV HN protein segment at the N-terminus and an AMPV5 HNprotein segment at the C-terminus. In some embodiments, the nucleic acidcomprises XbaI and MluI restriction endonuclease sites between nucleicacid sequence encoding phosphoprotein and matrix protein. In someembodiments, the chimeric F protein comprises at the C-terminus 53 aminoacid of NDV F protein from amino acid positions 501 to 553 of SEQ ID NO:28. In some embodiments, the chimeric HN protein comprises at theN-terminus 53 amino acids of NDV HN protein from amino acid positions 1to 53 of SEQ ID NO: 34. In some embodiments, the stabilizing segmentcomprises an amino acid sequence as set forth in SEQ ID NO: 20. In someembodiments, the stabilizing segment is encoded by a nucleic acidcomprising a nucleic acid sequence as set forth in SEQ ID NO: 35. Insome embodiments, the L protein comprises an amino acid sequence havingat least 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100%identity to the amino acid sequence as set forth in SEQ ID NO: 11. Insome embodiments, the chimeric F protein comprises an amino acidsequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%,99.9%, or 100% identity to the amino acid sequence of SEQ ID NO: 12. Insome embodiments, the chimeric HN protein comprises an amino acidsequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%,99.9%, or 100% identity to the amino acid sequence of SEQ ID NO: 13. Insome embodiments, the nucleic acid further comprises at least oneheterologous nucleic acid segment encoding a therapeutic agent operablylinked to a promoter capable of expressing the segment in a host cell.In some embodiments, the therapeutic agent comprises a SARS-CoV-2 spikeprotein. In some embodiments, the SARS-CoV-2 spike protein comprises anamino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%,99.5%, 99.9%, or 100% identity to the amino acid sequence of SEQ ID NO:6, 7, 29, 30, 31, or 41.

Methods and Uses

The term “infectious disease”, “transmissible disease” or “communicabledisease”, and their derivatives, as used herein, refer to or describe adisease or disorder resulted from an infection, for example, caused byinfectious agents including viruses, viroids, prions, bacteria,nematodes such as parasitic roundworms and pinworms, arthropods such asticks, mites, fleas, and lice, fungi such as ringworm, and othermacroparasites such as tapeworms and other helminths. Examples ofinfectious diseases include viral diseases such as viral hemorrhagicfevers such as Ebola and Marburg virus disease, gastroenteritis, denguefever, West Nile fever, yellow fever, influenza, respiratory syncytialvirus disease, Lassa fever, rabies, smallpox, cowpox, horsepox,monkeypox, Hantavirus pulmonary syndrome, Hendra virus disease, humanimmunodeficiency virus infection and acquired immunodeficiency diseasesyndrome, Hepatitis, Zika fever, Severe Acute Respiratory Syndrome(SARS), Middle East Respiratory Syndrome (MERS), Coronavirus disease2019 (COVID-19), infectious bronchitis, infectious laryngotracheitis,Rift Valley fever, porcine epidemic diarrhea, porcine transmissiblegastroenteritis, swine acute diarrhea syndrome, feline infectiousperitonitis, African swine fever, classical swine fever, and bacterialdiseases including drug resistant bacterial diseases such astuberculosis and methicillin-resistant Staphylococcus aureus infection,and drug resistant parasitic diseases such as malaria. In an embodimentof this disclosure, the infectious disease is a viral disease or abacterial disease. In an embodiment, the viral disease is viralhemorrhagic fever, gastroenteritis, dengue fever, West Nile fever,yellow fever, influenza, respiratory syncytial virus disease, Lassafever, rabies, smallpox, cowpox, horsepox, monkeypox, Hantaviruspulmonary syndrome, Hendra virus disease, human immunodeficiency virusinfection and acquired immunodeficiency disease syndrome, Hepatitis,Zika fever, SARS, MERS, COVID-19, infectious bronchitis, infectiouslaryngotracheitis, Rift Valley fever, porcine epidemic diarrhea, porcinetransmissible gastroenteritis, swine acute diarrhea syndrome, felineinfectious peritonitis, African swine fever, or classical swine fever.In an embodiment, the viral hemorrhagic fever is Ebola or Marburg virusdisease. In an embodiment, the bacterial disease is a drug resistantbacterial disease. In an embodiment, the drug resistant bacterialdisease is tuberculosis, methicillin-resistant Staphylococcus aureusinfection, or a drug resistant parasitic disease. In an embodiment, thedrug resistant parasitic disease is malaria. In an embodiment, theinfectious disease is COVID-19.

The term “cancer” and its derivates, as used herein, refers to a groupof diseases comprising cells having abnormal cell growth andmetastasized or the potential to metastasize, i.e. invade or spread toother parts of the body. For example, cancer includes but not limited topancreatic cancer, kidney cancer such as renal cell carcinoma,urogenital cancer such as urothelial carcinomas, melanoma, prostatecarcinoma, lung carcinomas such as non-small cell carcinoma, small cellcarcinoma, neuroendocrine carcinoma, or carcinoid tumor, breastcarcinomas such as ductal carcinoma, lobular carcinoma, or mixed ductaland lobular carcinoma, thyroid carcinomas such as papillary thyroidcarcinoma, follicular carcinoma, or medullary carcinoma, brain cancerssuch as meningioma, astrocytoma, glioblastoma, cerebellum tumors, ormedulloblastoma, ovarian carcinomas such as serous, mucinous, orendometrioid types carcinomas, cervical cancers such as squamous cellcarcinoma in situ, invasive squamous cell carcinoma, or endocervicaladenocarcinoma, uterine endometrial carcinoma such as endometrioid orserous and mucinous types carcinomas, primary peritoneal carcinoma,mesothelioma such as pleura or peritoneum mesothelioma, eye cancer suchas retinoblastoma, muscle cancer such as rhabdosarcoma orleiomyosarcoma, lymphomas, esophageal cancer such as adenocarcinoma orsquamous cell carcinoma, gastric cancers such as gastric adenocarcinomaor gastrointestinal stroma tumour (GIST), liver cancers such ashepatocellular carcinoma or bile duct cancer, small intestinal tumorssuch as small intestinal stromal tumor or carcinoid tumor, colon cancersuch as adenocarcinoma of the colon, colon high grade dysplasia, orcolon carcinoid tumor, testicular cancer, skin cancers such as melanomaor squamous cell carcinoma, or adrenal carcinoma.

The term “treating” and its derivatives, as used herein, refers toimproving the condition associated with a disease, such as reducing oralleviating symptoms associated with the condition or improving theprognosis or survival of the subject. The term “preventing” and itsderivatives, as used herein, refer to averting or delaying the onset ofthe disease, such as inhibiting or avoiding the advent of the disease,or vaccinated against the disease, or the lessening of symptoms upononset of the disease, in the subject. The term “prophylactic” shall havea corresponding meaning.

The term “subject” as used herein refers to any member of the animalkingdom, optionally a mammal, optionally a human. In an embodiment, thesubject is a mammal. In an embodiment, the subject is a human, anon-human primate, a rodent, a feline, a canine, an ovine, a bovine, aporcine, a caprine, an equine, a lupine, a vulpine, or a mustelid. In anembodiment, the subject is human. In an embodiment, the Mustela is aweasel, a polecat, stoats, a ferret or a mink. In an embodiment, thesubject is a mink.

Accordingly, the present disclosure provides a method of treating orpreventing a disease in a subject, comprising administering anengineered NDV vector comprising a nucleic acid having a nucleic acidsequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%,99.5%, 99.9% or 100% identical to the nucleic acid sequence of any oneof SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42, and wherein the nucleicacid comprises or further comprises at least one heterologous nucleicacid segment encoding a therapeutic agent operably linked to a promotercapable of expressing the segment in a host cell. In an embodiment, thenucleic acid comprises a nucleic acid sequence encoding an L proteinhaving a stabilizing segment. In an embodiment, the host cell isselected from the group consisting of a human, primate, murine, feline,canine, ovine, bovine, porcine, caprine, equine, lupine, vulpine, andMustela host cell. In a further embodiment, the promoter is capable ofexpressing the at least one heterologous nucleic acid segment encodingthe therapeutic agent in muscle, airway, or lung cells. In anembodiment, the therapeutic agent is any therapeutic agent as describedherein. In an embodiment, the disease is any disease described herein.

The engineered NDV vector of the present disclosure is also useful foreliciting an immune response. According, also provided is a method foreliciting an immune response in a subject comprising administering anengineered NDV vector comprising a nucleic acid having a nucleic acidsequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%,99.5%, 99.9% or 100% identical to the nucleic acid sequence of any oneof SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42, wherein the nucleicacid comprises a nucleic acid sequence encoding an L protein having astabilizing segment, wherein the nucleic acid comprises XbaI and MluIrestriction endonuclease sites between nucleic acid sequence encodingphosphoprotein and matrix protein. In an embodiment, the nucleic acidcomprises or further comprises at least one heterologous nucleic acidsegment encoding a therapeutic agent operably linked to a promotercapable of expressing the segment in a host cell. In an embodiment, thetherapeutic agent is an immunogenic agent. In an embodiment, theimmunogenic agent is SARS-CoV-2 spike protein or fragment thereof. In anembodiment, the nucleic acid comprises a nucleic acid sequence that isat least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or100% identical to the nucleic acid sequence of any one of SEQ ID NO: 2,3, 4, 18, 19, 23, 27, or 42. In an embodiment, the immunogenic agentactivates B-cells, CD4+ T-cells and/or CD8+ T-cells.

Also provided is use of an engineered NDV vector for eliciting an immuneresponse in a subject, wherein the engineered NDV vector comprises anucleic acid having a nucleic acid sequence that is at least 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% A or 100% identical tothe nucleic acid sequence of any one of SEQ ID NO: 1-5, 9, 10, 18, 19,23, 27, or 42, wherein the nucleic acid comprises a nucleic acidsequence encoding an L protein having a stabilizing segment wherein thenucleic acid comprises or further comprises at least one heterologousnucleic acid segment encoding a therapeutic agent operably linked to apromoter capable of expressing the segment in a host cell, and whereinthe nucleic acid comprises XbaI and MluI restriction endonuclease sitesbetween nucleic acid sequence encoding phosphoprotein and matrixprotein. In an embodiment, the at least one heterologous nucleic acidsegment encodes a therapeutic agent operably linked to a promotercapable of expressing the segment in a host cell. In an embodiment, thetherapeutic agent is an immunogenic agent. In an embodiment, theimmunogenic agent is SARS-CoV-2 spike protein or fragment thereof. In anembodiment, the nucleic acid comprises a nucleic acid sequence that isat least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or100% identical to the nucleic acid sequence of any one of SEQ ID NO: 2,3, 4, 18, or 19. In an embodiment, the immunogenic agent activatesB-cells, CD4+ T-cells and/or CD8+ T-cells.

Further provided is use of an engineered NDV vector in the manufactureof a medicament for eliciting an immune response in a subject, whereinthe engineered NDV vector comprises a nucleic acid having a nucleic acidsequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%,99.5%, 99.9% or 100% identical to the nucleic acid sequence of any oneof SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42, wherein the nucleicacid comprises a nucleic acid sequence encoding an L protein having astabilizing segment, wherein the nucleic acid comprises or furthercomprises at least one heterologous nucleic acid segment encoding atherapeutic agent operably linked to a promoter capable of expressingthe segment in a host cell, and wherein the nucleic acid comprises XbaIand MluI restriction endonuclease sites between nucleic acid sequenceencoding phosphoprotein and matrix protein. In an embodiment, the atleast one heterologous nucleic acid segment encodes a therapeutic agentoperably linked to a promoter capable of expressing the segment in ahost cell. In an embodiment, the therapeutic agent is an immunogenicagent. In an embodiment, the immunogenic agent is SARS-CoV-2 spikeprotein or fragment thereof. In an embodiment, the nucleic acidcomprises a nucleic acid sequence that is at least 75%, 80%, 85%, 90%,95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% A or 100% identical to the nucleicacid sequence of any one of SEQ ID NO: 2, 3, 4, 18, or 19. In anembodiment, the immunogenic agent activates B-cells, CD4+ T-cells and/orCD8+ T-cells.

Even further provided is an engineered NDV vector for use in elicitingan immune response, wherein the engineered NDV vector comprises anucleic acid having a nucleic acid sequence that is at least 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% A or 100% identical tothe nucleic acid sequence of any one of SEQ ID NO: 1-5, 9, 10, 18, 19,23, 27, or 42, wherein the nucleic acid comprises a nucleic acidsequence encoding an L protein having a stabilizing segment. wherein thenucleic acid comprises or further comprises at least one heterologousnucleic acid segment encoding a therapeutic agent operably linked to apromoter capable of expressing the segment in a host cell, and whereinthe nucleic acid comprises XbaI and MluI restriction endonuclease sitesbetween nucleic acid sequence encoding phosphoprotein and matrixprotein. In an embodiment, the at least one heterologous nucleic acidsegment encodes a therapeutic agent operably linked to a promotercapable of expressing the segment in a host cell. In an embodiment, thetherapeutic agent is an immunogenic agent. In an embodiment, theimmunogenic agent is SARS-CoV-2 spike protein or fragment thereof. In anembodiment, the nucleic acid comprises a nucleic acid sequence that isat least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or100% identical to the nucleic acid sequence any one of SEQ ID NO: 2, 3,4, 18, or 19. In an embodiment, the immunogenic agent activates B-cells,CD4+ T-cells and/or CD8+ T-cells.

The ability of the engineered NDV vector of the present disclosure toactivate an immune response is useful for its use as a vaccine or animmunogenic composition. Accordingly, also provided is a method forvaccination, the method comprises administering a vaccine comprising anengineered NDV vector having a nucleic acid comprises a nucleic acidsequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%,99.5%, 99.9% or 100% identical to the nucleic acid sequence of any oneof SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42, wherein the nucleicacid comprises a nucleic acid sequence encoding an L protein having astabilizing segment. wherein the nucleic acid comprises or furthercomprises at least one heterologous nucleic acid segment encoding atherapeutic agent operably linked to a promoter capable of expressingthe segment in a host cell, and wherein the nucleic acid comprises XbaIand MluI restriction endonuclease sites between nucleic acid sequenceencoding phosphoprotein and matrix protein. In an embodiment, the atleast one heterologous nucleic acid segment encoding a therapeutic agentoperably linked to a promoter capable of expressing the segment in ahost cell. In an embodiment, the therapeutic agent is an immunogenicagent. In an embodiment, the immunogenic agent is SARS-CoV-2 spikeprotein or fragment thereof. In an embodiment, the nucleic acidcomprises a nucleic acid sequence that is at least 75%, 80%, 85%, 90%,95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or 100% identical to the nucleicacid sequence of any one of SEQ ID NO: 2, 3, 4, 18, or 19. In anembodiment, the immunogenic agent activates B-cells, CD4+ T-cells and/orCD8+ T-cells.

Also provided is use of a vaccine comprising an engineered NDV vectorfor vaccinating a subject, wherein the engineered NDV vector comprises anucleic acid having a nucleic acid sequence that is at least 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or 100% identical to thenucleic acid sequence of any one of SEQ ID NO: 1-5, 9, 10, 18, 19, 23,27, or 42, wherein the nucleic acid comprises a nucleic acid sequenceencoding an L protein having a stabilizing segment, wherein the nucleicacid comprises or further comprises at least one heterologous nucleicacid segment encoding a therapeutic agent operably linked to a promotercapable of expressing the segment in a host cell, and wherein thenucleic acid comprises XbaI and MluI restriction endonuclease sitesbetween nucleic acid sequence encoding phosphoprotein and matrixprotein. In an embodiment, the at least one heterologous nucleic acidsegment encoding a therapeutic agent operably linked to a promotercapable of expressing the segment in a host cell. In an embodiment, thetherapeutic agent is an immunogenic agent. In an embodiment, theimmunogenic agent is SARS-CoV-2 spike protein or fragment thereof. In anembodiment, the nucleic acid comprises a nucleic acid sequence that isat least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or100% identical to the nucleic acid sequence of any one of SEQ ID NO: 2,3, 4, 18, or 19. In an embodiment, the immunogenic agent activatesB-cells, CD4+ T-cells and/or CD8+ T-cells.

Further provided is use of a vaccine comprising an engineered NDV vectorin the manufacture of a medicament for vaccinating a subject, whereinthe engineered NDV vector comprises a nucleic acid having a nucleic acidsequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%,99.5%, 99.9% or 100% identical to the nucleic acid sequence of any oneof SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42, wherein the nucleicacid comprises a nucleic acid sequence encoding an L protein having astabilizing segment, wherein the nucleic acid comprises or furthercomprises at least one heterologous nucleic acid segment encoding atherapeutic agent operably linked to a promoter capable of expressingthe segment in a host cell, and wherein the nucleic acid comprises XbaIand MluI restriction endonuclease sites between nucleic acid sequenceencoding phosphoprotein and matrix protein. In an embodiment, the atleast one heterologous nucleic acid segment encodes a therapeutic agentoperably linked to a promoter capable of expressing the segment in ahost cell. In an embodiment, the therapeutic agent is an immunogenicagent. In an embodiment, the immunogenic agent is SARS-CoV-2 spikeprotein or fragment thereof. In an embodiment, the nucleic acidcomprises a nucleic acid sequence that is at least 75%, 80%, 85%, 90%,95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% A or 100% identical to the nucleicacid sequence of any one of SEQ ID NO: 2, 3, 4, 18, or 19. In anembodiment, the immunogenic agent activates B-cells, CD4+ T-cells and/orCD8+ T-cells.

Even further provided is a vaccine comprising an engineered NDV vectorfor use in vaccinating a subject, wherein the engineered NDV vectorcomprises a nucleic acid having a nucleic acid sequence that is at least75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% A or 100%identical to the nucleic acid sequence of any one of SEQ ID NO: 1-5, 9,10, 18, 19, 23, 27, or 42, wherein the nucleic acid comprises a nucleicacid sequence encoding an L protein having a stabilizing segment,wherein the nucleic acid comprises or further comprises at least oneheterologous nucleic acid segment encoding a therapeutic agent operablylinked to a promoter capable of expressing the segment in a host cell,and wherein the nucleic acid comprises XbaI and MluI restrictionendonuclease sites between nucleic acid sequence encoding phosphoproteinand matrix protein. In an embodiment, the at least one heterologousnucleic acid segment encodes a therapeutic agent operably linked to apromoter capable of expressing the segment in a host cell. In anembodiment, the therapeutic agent is an immunogenic agent. In anembodiment, the immunogenic agent is SARS-CoV-2 spike protein orfragment thereof. In an embodiment, the nucleic acid comprises a nucleicacid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%,99%, 99.5%, 99.9% or 100% identical to the nucleic acid sequence of anyone of SEQ ID NO: 2, 3, 4, 18, 19, 23, 27, or 42. In an embodiment, theimmunogenic agent activates B-cells, CD4+ T-cells and/or CD8+ T-cells.

Also provided is a method for administering an immunogenic compositionin a subject, the method comprises administering an immunogeniccomposition comprising an engineered NDV vector having a nucleic acidcomprises a nucleic acid sequence that is at least 75%, 80%, 85%, 90%,95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% A or 100% identical to the nucleicacid sequence of any one of SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or42, wherein the nucleic acid comprises a nucleic acid sequence encodingan L protein having a stabilizing segment, wherein the nucleic acidcomprises or further comprises at least one heterologous nucleic acidsegment encoding a therapeutic agent operably linked to a promotercapable of expressing the segment in a host cell, and wherein thenucleic acid comprises XbaI and MluI restriction endonuclease sitesbetween nucleic acid sequence encoding phosphoprotein and matrixprotein. In an embodiment, the therapeutic agent is an immunogenicagent. In an embodiment, the immunogenic agent is SARS-CoV-2 spikeprotein or fragment thereof. In an embodiment, the nucleic acidcomprises a nucleic acid sequence that is at least 75%, 80%, 85%, 90%,95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% A or 100% identical to the nucleicacid sequence of any one of SEQ ID NO: 2, 3, 4, 18, or 19. In anembodiment, the immunogenic agent activates B-cells, CD4+ T-cells and/orCD8+ T-cells.

Also provided is use of an immunogenic composition comprising anengineered NDV vector for eliciting an immune response in a subject,wherein the engineered NDV vector comprises a nucleic acid having anucleic acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%,97%, 98%, 99%, 99.5%, 99.9% or 100% identical to the nucleic acidsequence of any one of SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42,wherein the nucleic acid comprises a nucleic acid sequence encoding an Lprotein having a stabilizing segment, wherein the nucleic acid comprisesor further comprises at least one heterologous nucleic acid segmentencoding a therapeutic agent operably linked to a promoter capable ofexpressing the segment in a host cell, and wherein the nucleic acidcomprises XbaI and MluI restriction endonuclease sites between nucleicacid sequence encoding phosphoprotein and matrix protein. In anembodiment, the therapeutic agent is an immunogenic agent. In anembodiment, the immunogenic agent is SARS-CoV-2 spike protein orfragment thereof. In an embodiment, the nucleic acid comprises a nucleicacid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%,99%, 99.5%, 99.9% or 100% identical to the nucleic acid sequence of anyone of SEQ ID NO: 2, 3, 4, 18, 19, 23, 27, or 42. In an embodiment, theimmunogenic agent activates B-cells, CD4+ T-cells and/or CD8+ T-cells.

Further provided is use of an immunogenic composition comprising anengineered NDV vector in the manufacture of a medicament for elicitingan immune response in a subject, wherein the engineered NDV vectorcomprises a nucleic acid having a nucleic acid sequence that is at least75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% A or 100%identical to the nucleic acid sequence of any one of SEQ ID NO: 1-5, 9,10, 18, 19, 23, 27, or 42, wherein the nucleic acid comprises a nucleicacid sequence encoding an L protein having a stabilizing segment,wherein the nucleic acid comprises or further comprises at least oneheterologous nucleic acid segment encoding a therapeutic agent operablylinked to a promoter capable of expressing the segment in a host cell,and wherein the nucleic acid comprises XbaI and MluI restrictionendonuclease sites between nucleic acid sequence encoding phosphoproteinand matrix protein. In an embodiment, the therapeutic agent is animmunogenic agent. In an embodiment, the immunogenic agent is SARS-CoV-2spike protein or fragment thereof. In an embodiment, the nucleic acidcomprises a nucleic acid sequence that is at least 75%, 80%, 85%, 90%,95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or 100% identical to the nucleicacid sequence of any one of SEQ ID NO: 2, 3, 4, 18, or 19. In anembodiment, the immunogenic agent activates B-cells, CD4+ T-cells and/orCD8+ T-cells.

Even further provided is an immunogenic composition comprising anengineered NDV vector for use in eliciting an immune response in asubject, wherein the engineered NDV vector comprises a nucleic acidhaving a nucleic acid sequence that is at least 75%, 80%, 85%, 90%, 95%,96%, 97%, 98%, 99%, 99.5%, 99.9% or 100% identical to the nucleic acidsequence of any one of SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42,wherein the nucleic acid comprises a nucleic acid sequence encoding an Lprotein having a stabilizing segment, wherein the nucleic acid comprisesor further comprises at least one heterologous nucleic acid segmentencoding a therapeutic agent operably linked to a promoter capable ofexpressing the segment in a host cell, and wherein the nucleic acidcomprises XbaI and MluI restriction endonuclease sites between nucleicacid sequence encoding phosphoprotein and matrix protein. In anembodiment, the therapeutic agent is an immunogenic agent. In anembodiment, the immunogenic agent is SARS-CoV-2 spike protein orfragment thereof. In an embodiment, the nucleic acid comprises a nucleicacid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%,99%, 99.5%, 99.9% A or 100% identical to the nucleic acid sequence anyone of SEQ ID NO: 2, 3, 4, 18, 19, 23, 27, or 42. In an embodiment, theimmunogenic agent activates B-cells, CD4+ T-cells and/or CD8+ T-cells.

The engineered NDV vector can function as a delivery vehicle thatdelivers heterologous nucleic acid segment (“payloads”) encoding atherapeutic agent for treating or preventing a disease such as aninfectious. In one embodiment, the infectious disease is selected fromthe group consisting of viral diseases such as viral hemorrhagic fevers,Ebola, Marburg virus disease, gastroenteritis, dengue fever, West Nilefever, yellow fever, influenza, respiratory syncytial virus disease,Lassa fever, rabies, smallpox, cowpox, horsepox, monkeypox, Hantaviruspulmonary syndrome, Hendra virus disease, human immunodeficiency virusdisease and acquired immunodeficiency disease syndrome, Hepatitis, Zikafever, optionally Ebola or Marburg virus disease, Severe AcuteRespiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS),Coronavirus disease 2019 (COVID-19), and bacterial diseases includingdrug resistant bacterial diseases such as tuberculosis andmethicillin-resistant Staphylococcus aureus infection, and drugresistant parasitic diseases such as malaria. In an embodiment, theinfectious disease is COVID-19.

The immune response can be independent of expression of a therapeuticagent such as an immunogenic agent. For example, the engineered NDVvector disclosed herein can activate NK cells in a subject bearingtumour. In some embodiments, the immune response comprises activation ofNK cells. In some embodiments, the activation of NK cells comprisesproduction of CD69, PD-L1, Granzyme B and/or IFNgamma. Such an immuneresponse is useful for the treatment of, for example, cancer, such thatthe engineered NDV vector of the present disclosure is also useful as ananti-cancer agent. According, also provided is a method of treatingcancer in a subject, comprising administering an engineered NDV vectorcomprising a nucleic acid having a nucleic acid sequence that is atleast 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or 100%identical to the nucleic acid sequence of any one of SEQ ID NO: 1, 5, 9,or 10.

Also provided is use of an engineered NDV vector for treating cancer ina subject, wherein the engineered NDV vector comprises a nucleic acidhaving a nucleic acid sequence that is at least 75%, 80%, 85%, 90%, 95%,96%, 97%, 98%, 99%, 99.5%, 99.9% or 100% identical to the nucleic acidsequence of any one of SEQ ID NO: 1, 5, 9, or 10.

Further provided is use of an engineered NDV vector in the manufactureof a medicament for treating cancer in a subject, wherein the engineeredNDV vector comprises a nucleic acid having a nucleic acid sequence thatis at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or100% identical to the nucleic acid sequence of any one of SEQ ID NO: 1,5, 9, or 10.

Even further provided is an engineered NDV vector for use in treatingcancer in a subject, wherein the engineered NDV vector comprises anucleic acid having a nucleic acid sequence that is at least 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or 100% identical to thenucleic acid sequence of any one of SEQ ID NO: 1, 5, 9, or 10.

In some embodiments, the engineered NDV vector comprises a nucleic acidhaving a nucleic acid sequence that is at least 75%, 80%, 85%, 90%, 95%,96%, 97%, 98%, 99%, 99.5%, 99.9% A or 100% identical to the nucleic acidsequence of SEQ ID NO: 9, 10, 23, or 27. In some embodiments, the canceris pancreatic cancer, kidney cancer such as renal cell carcinoma,urogenital cancer such as urothelial carcinomas, melanoma, prostatecarcinoma, lung carcinomas such as non-small cell carcinoma, small cellcarcinoma, neuroendocrine carcinoma, or carcinoid tumor, breastcarcinomas such as ductal carcinoma, lobular carcinoma, or mixed ductaland lobular carcinoma, thyroid carcinomas such as papillary thyroidcarcinoma, follicular carcinoma, or medullary carcinoma, brain cancerssuch as meningioma, astrocytoma, glioblastoma, cerebellum tumors, ormedulloblastoma, ovarian carcinomas such as serous, mucinous, orendometrioid types carcinomas, cervical cancers such as squamous cellcarcinoma in situ, invasive squamous cell carcinoma, or endocervicaladenocarcinoma, uterine endometrial carcinoma such as endometrioid orserous and mucinous types carcinomas, primary peritoneal carcinoma,mesothelioma such as pleura or peritoneum mesothelioma, eye cancer suchas retinoblastoma, muscle cancer such as rhabdosarcoma orleiomyosarcoma, lymphomas, esophageal cancer such as adenocarcinoma orsquamous cell carcinoma, gastric cancers such as gastric adenocarcinomaor gastrointestinal stroma tumour (GIST), liver cancers such ashepatocellular carcinoma or bile duct cancer, small intestinal tumorssuch as small intestinal stromal tumor or carcinoid tumor, colon cancersuch as adenocarcinoma of the colon, colon high grade dysplasia, orcolon carcinoid tumor, testicular cancer, skin cancers such as melanomaor squamous cell carcinoma, or adrenal carcinoma. In an embodiment, thecancer is an ovarian cancer.

The use or administration of an engineered NDV vector to a subjectcomprises ingestion, instillation such as intranasally, inhalation suchas via aerosol, or injection. The route of injection includes but is notlimited to intradermal, subcutaneous, intramuscular, intravenous,intraosseous, intraperitoneal, intrathecal, epidural, intracardiac,intraarticular, intracavernous, intravitreal, intracerebral,intracerebroventricular, intratracheal or intraportal. In an embodiment,the engineered NDV vector is administered or used intravenously,intranasally, intratracheal, intramuscularly, or via aerosol. In anembodiment, the engineered NDV vector is administered or usedintranasally. In an embodiment, the engineered NDV vector isadministered or used intramuscularly. In an embodiment, the engineeredNDV vector is delivered to muscle, airway, or lung cells or tissues.

The present disclosure further provides a method of producing a proteinin vivo in a subject, comprising delivering or introducing into thesubject an engineered NDV vector comprising a nucleic acid having anucleic acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%,97%, 98%, 99%, 99.5%, 99.9% or 100% identical to the nucleic acidsequence of any one of SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42,wherein the nucleic acid comprises a nucleic acid sequence encoding an Lprotein having a stabilizing segment, wherein the nucleic acid comprisesor further comprises at least one heterologous nucleic acid segmentencoding a protein operably linked to a promoter capable of expressingthe segment in a host cell, and wherein the nucleic acid comprises XbaIand MluI restriction endonuclease sites between nucleic acid sequenceencoding phosphoprotein and matrix protein. In an embodiment, thenucleic acid comprises a nucleic acid sequence that is at least 75%,80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or 100% identicalto the nucleic acid sequence of SEQ ID NO: 9, 10, 23, or 27.

In addition, the present disclosure provides a method of producing atleast one protein in vitro in a host cell, comprising introducing intothe host cell an engineered NDV vector comprising a nucleic acid havinga nucleic acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%,97%, 98%, 99%, 99.5%, 99.9% or 100% identical to the nucleic acidsequence of any one of SEQ ID NO: 1-5, 9, 10, 18, 19, 23, 27, or 42,wherein the nucleic acid comprises a nucleic acid sequence encoding an Lprotein having a stabilizing segment, wherein the nucleic acid comprisesor further comprises at least one heterologous nucleic acid segmentencoding a protein operably linked to a promoter capable of expressingthe segment in a host cell, and wherein the nucleic acid comprises XbaIand MluI restriction endonuclease sites between nucleic acid sequenceencoding phosphoprotein and matrix protein. In an embodiment, theprotein is any protein described herein. The skilled person can readilyrecognize the suitable production or manufacturing methods for producingproteins such as therapeutic agents using the engineered NDV vector asdescribed herein. In an embodiment, the nucleic acid comprises a nucleicacid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%,99%, 99.5%, 99.9% or 100% identical to the nucleic acid sequence of SEQID NO: 9, 10, 23, or 27.

Also provided is a method for selecting a stable engineered NDV vectorgenome. Inventors have developed a visual screening tool for selectingstable engineered clones based on their growth pattern on Luria-Bertani(LB) plates. When cloning transgenes (e.g. viral antigen for vaccinepurposes) into the NDV genome and screening for colonies that containthe full-length NDV genome plasmid with the correct insert, thetransformed bacteria often grow as both large and small colonies. Thelarge colonies are visible after 16 hours whereas the smaller coloniesneed to grow for at least 24 hours before they are large enough toinoculate a liquid culture. The large colonies often contain mutated NDVgenome plasm ids, whereas the small colonies invariably contain stableNDV clones and are thus selected for growth in liquid culture.Accordingly, also provided is a method for selecting an engineered NDVvector genome comprising a stabilizing segment in L gene, the methodcomprises:

-   -   a) growing bacterial cells comprising an engineered NDV vector        genome plasmid in growth medium broth;    -   b) growing the bacterial cells on an agar-growth medium, wherein        the agar-growth medium comprises a selection agent;    -   c) identifying small bacterial cell colonies having about 0.5 mm        to about 1 mm in diameter after at least 24 hours of growth;    -   d) repeating step a) to step c) two to nine times to enrich for        small bacterial cell colonies; and    -   e) isolating the engineered NDV vector genome from the small        bacterial cell colonies,    -   wherein the small bacterial cells colonies comprise stable        engineered NDV vector genome having the stabilizing segment in L        gene.

In an embodiment, the growth medium broth is a Luria Bertani (LB) broth.In an embodiment, the agar-growth medium is agar-Luria Bertani (LB). Inan embodiment, the selection agent is an antibiotic. In an embodiment,the antibiotic is kanamycin. In an embodiment, the stabilizing segmentcomprises an amino acid sequence as set forth in SEQ ID NO: 20. In anembodiment, the stabilizing segment is encoded by a nucleic acidcomprising a nucleic acid sequence as set forth in SEQ ID NO: 35. In anembodiment, the stable engineered NDV vector genome encodes afull-length L protein (SEQ ID NO: 11). In an embodiment, the bacterialcells are E. coli. In an embodiment, the E. coli is an E. coli strainStellar, NEBStable, or GT116.

The following non-limiting Examples are illustrative of the presentdisclosure:

Example 1A. Development of NDV-FLS and NDV-A19S Immunogens UsingEngineered Newcastle Disease Virus Vectors Expressing SARS-CoV-2 SpikeProteins Materials and Methods Engineered NDV Vector

The full-length cDNA genome of lentogenic NDV LaSota strain wassynthetically designed based on accession AF077761.1 to contain a GFPreporter gene and essential NDV-specific RNA transcriptional signals,flanked by a 5′ XbaI site and a 3′ MluI site at position 3143 nucleotidebetween the P and M genes. Unique restriction sites between the P geneand the M gene were chosen because transgenes expressed between thesesites are highly expressed and these restriction sites do not interferewith the stability of the recombinant virus. A leucine to alaninemutation at position 289 was also introduced into the Fusion gene. Toconstruct recombinant NDV expressing SARS-CoV-2 Spike protein, forward5′GCACCGAGTTCCCCCTCTAGATTAGAAAAAATACGG GTAGAACCGCCAC-3′ (SEQ ID NO: 21)and reverse 5′GTTGGACCTTGGGTAC GCGTTTATCAGGTGTAGTGCAGCTTCAC-3′ (SEQ IDNO: 22) primers were used to amplify human codon optimized SARS-CoV-2full length spike protein. Additionally, a 19 amino acid truncated formof the Spike protein (SΔ19) was amplified using the above forward primer(SEQ ID NO: 21) and a reverse 5′GTTGGACCTTGGGTACGCGTTTATCATCAGCAGCAAGAGCCGCAAGAACAAC-3′ (SEQ ID NO: 24).Infusion Cloning™ was used to insert transgenes into the NDV backboneaccording to the manufacturer's protocol (Takara Bio USA), with the 5′end of the primer including 15 bp of homology with each end of thelinearized vector including the XbaI or MluI sites. Viruses were rescuedfrom cDNA, amplified and purified using methods described previously(Santry, L. A. et al., 2017) and confirmed by RT-PCR and sequencing.

DF-1 Infection Protocol

DF-1 cells (ATCC CRL-12203) were seeded into 6-well plates at 1.5×10⁶cells/well in 1 mL of DMEM supplemented with 2% bovine calf serum (BCS)and 5% allantoic fluid. After adherence, the cells were infected witheither NDV-FLS, -Δ19S or -GFP at MOI of 1 and 10 in replicate plates.The plates were incubated at 37° C. One day post infection, thereplicate plates were observed under an inverted phase contrastmicroscope to examine and document cytopathic effect (CPE) withphotographs. Subsequently, one set of replicate plates was collected forprotein extraction and Western blot analysis, and the second set ofreplicate plates was used for immunofluorescence assay (IFA).

Immunofluorescence Assay

Approximately 1 day post infection, old media were removed and cellswere rinsed twice with phosphate-buffered saline (PBS). Cells were thenfixed in 4% paraformaldehyde (PFA) for 15 minutes at room temperature(RT). After fixation, cells were washed three times with PBS-T (PBS-1%tween) for 5 minutes each. The cells were then permeabilized in 0.1%NP-40 for 10 minutes at RT followed by three washes with PBS-T for 5minutes each. Subsequently, cells were blocked in blocking buffer [5%(v/v) normal goat serum in PBS-T] either for one hour at RT or overnightat 4° C. After blocking, cells were incubated in primary mouse anti-NDV(NBP2-11633; Novus Biologicals) diluted 1:2000 in blocking buffer forone hour at RT (or overnight at 4° C.). Following the primary antibodyincubation, cells were washed three times with PBS-T for 5 minutes eachand then incubated with secondary goat-anti-mouse-488 (Invitrogen,ThermoFisher) diluted in 1:1000 in PBS-T for one hour at RT in the dark.Following secondary antibody incubation, cells were once more washed 3times with PBS-T for 5 minutes each. After the final wash was removed,PBS-T was added to keep cells submerged under solution, and cells wereimaged using an Axio observer inverted fluorescent microscope.

SDS-PAGE (Denaturing) and Western Blot Analysis

Infected DF-1 cells were washed with PBS and lysed inradioimmunoprecipitation assay (RIPA) buffer (50 mM Tris-HCl pH 8, 150mM NaCl, 1% NP-40, 0.5% sodium deoxycholate, 0.1% sodium dodecylsulfate, 1× protease inhibitor cocktail) for 30 min on ice. Followinglysis, cell lysates were centrifuged at 10,000×g for 15 min at 4° C. Thesupernatants were transferred to a new collection tube and debris wasdiscarded. Protein amount in the supernatants were quantified using thePierce BCA Protein Assay Kit (ThermoFisher) according to themanufacturer's instructions. For SDS-PAGE, cell lysates (mixed with 6×loading dye containing and 30% β-mercaptoethanol) were heated at 95° C.for 10 min to denature proteins, followed by cooling on ice. Protein,with amounts ranging from 5 μg to 70 μg depending on experiment, wereloaded into wells of 4% stacking/12% resolving gels. The same proteinamount of each sample was loaded within each experiment. Proteins wereresolved at 120 V for 1.5 h in running buffer (0.025 mM Tris-base, 0.192M glycine, 0.1% SDS), followed by semi-dry transfer to a 0.2 μm PVDFmembrane for 30 min using the BioRad Trans-Blot Turbo Transfer Systemand BioRad proprietary buffer (BioRad Trans-Blot Turbo RTA Mini PVDFTransfer Kit). Following transfer, the rest of the protocol wasperformed as previously described (Pham P H et al., 2020). All washsteps were performed with PBS-T. The primary antibodies were either themouse anti-NDV antibody (dilution: 1:5000; NBP2-11633; NovusBiologicals), rabbit anti-SARS spike protein antibody (dilution: 1:1000;NB100-56578; Novus Biologicals), or mouse anti-beta actin antibody(diluted 1:1000; MA5-15739; ThermoFisher). Primary antibodies wereincubated overnight at 4° C. The secondary antibodies were either goatanti-rabbit or goat anti-mouse IgG conjugated to horseradish peroxidase(diluted 1:2000; ThermoFisher). Secondary antibodies were incubated for1 to 3 h at RT. Protein was detected using the Pierce SuperSignal WestPico PLUS Chemiluminescent Substrate (ThermoFisher) and a BioRadChemiDoc MP Imaging System (BioRad Image Lab 6.0.1. software).

Determination of Mean Death Time (MDT)

The MDT was determined for three viruses: NDV-FLS, -SΔ19, and -GFP. Thevirus stocks were equalized to the starting titre of 6.14×10⁶ FFU/mL.Each virus was diluted in a 10-fold 1 mL serial dilution series from10⁻¹ to 10⁻⁸ in PBS. To determine the MDT, virus dilutions from 10⁻⁴ to10⁻⁸ were chosen to be inoculated into SPF eggs (Canadian FoodInspection Agency) at 9 to 11 days of embryonation. For each of thethree viruses, a total of 50 eggs were used for two replicate MDTexperiments (25 eggs per replicate), which were done in the same day butseparated by 3 to 4 hours between replicates. Of the 25 eggs in eachreplicate MDT experiment, five replicate eggs received 100 μL of 10⁻⁴diluted virus, five received 100 μL of 10⁻⁵ diluted virus, five received100 μL of 10⁻⁸ diluted virus, five received 100 μL of 10⁻⁷ diluted virusand five received 100 μL of 10⁻⁸ diluted virus. For the entire MDTexperiment involving all three viruses, a total of 150 eggs were used.After virus inoculation, the eggs were incubated for up to 7 days andchecked and scored twice daily for embryo mortality. Allantoic fluid wascollected from dead embryos to check for presence of NDV byhemagglutination assay (HA). If no MDT was reached by the end of theexperiment (7 days post inoculation), then HA was performed on allantoicfluid collected from eggs inoculated with the virus dilution containingthe highest virus amount (10⁻⁴) to confirm presence of NDV in eggscontaining embryos that did not die (as defined by the AVIS Consortium,seehttp://www.fao.org/ag/againfo/programmes/en/empres/gemp/avis/A160-newcastle/mod0/0344-mdt-tests.html).

Hemagglutination Assay (HA)

For the HA, allantoic fluid (from eggs inoculated with NDV) was dilutedin a 2-fold 100 μL serial dilution series from 2⁻¹ (e.g. 50 μL ofallantoic fluid and 50 μL of PBS) to 2⁻⁷ in PBS, in duplicate wells of a96-well V-bottom plates. At the last dilution of 2⁻⁷, after mixing, 50μL of the mixture was discarded, leaving 50 μL remaining in these wellsand the wells of the other dilutions. The above procedure was repeatedfor PBS alone and for allantoic fluid from uninfected control eggs;these served as negative controls for the HA. Once serial dilution wascompleted, 50 μL of 1% chicken red blood cells (diluted in PBS) wasadded to each well. The plates were incubated at RT for 45 min followedby scoring of the plates and documentation by photographs.

Rescue of SARS-CoV-2 Spike Protein Pseudotyped Lentiviral Particles

HEK 293T (human kidney cells, ATCC CRL-11268) cells grown in DMEM with10% FBS and 1% penicillin/streptomycin were seeded in a 10 cm cellculture dish so that they would be 60-70% confluent the following day.16-24 h post-seeding, cells were transfected using PolyJet™ Reagent(SignaGen Laboratories) in a 1:1 ratio of reagent-to-DNA with 6.7 μg ofeach of the following plasm ids: pSin-EF1α-luciferase, psPAX2 (DidierTrono; Addgene plasmid #12260; http://n2t.net/addgene:12260;RRID:Addgene_12260), and pCASI-SARS-CoV-2-Spike-Δ19. The following daythe media was changed to fresh complete media. Starting at 48 hourspost-media change, lentivirus was collected twice per day by changingmedia and replacing with complete media. Lentivirus was collected until96 hours post-media change for a total 5 collections. Lentiviruscollections were pooled, filtered through a 0.45 μm PES filter andfrozen as aliquots at −80° C.

Assessment of Luciferase Activity

1.25×10⁴ HEK293T-hACE2 cells (Dr. Paul Spagnuolo, University of Guelph)were seeded per well in a 96-well plate and left to adhere overnight.The following day, media was removed and replaced with 40 μL of freshcomplete media. Cells were then transduced with 60 μL of lentivirus,along with polybrene at a final concentration of 8 μg/mL. 60 hourspost-transduction, luciferase activity was measured using the Pierce™Firefly Luciferase Glow Assay Kit (Thermo Scientific) as permanufacturer's instructions. Luciferase readings were measured in whiteplates using an Enspire® Multimode Plate Reader (Perkin Elmer).

Statistical Analysis

All results were analyzed and plotted using GraphPad Prism 8 Software.Statistical significance was assessed using Mann-Whitney test, one-wayanalysis of variance (ANOVA), two-way ANOVA where appropriate.

Results

A fully synthetic molecular clone was engineered from lentogenic NDV(LaSota strain, Genbank accession AF077761.1) encoding a T7 promoterfollowed by three non-templated G's, unique XbaI and MluI restrictionsites between the phosphoprotein (P) and the matrix (M) genes tofacilitate transgene insertion, and a T7 terminator sequence. Also, anL289A mutation in the fusion (F) gene was also incorporated for enhancedfusion (Sergei, T. A et al 2000), and a self-cleaving hepatitis deltavirus (HDV) ribozyme sequence was added to ensure adherence to the “ruleof six” by self-cleaving immediately at the end of the viral antigenomictranscript (Kolakofsky, D., et al., 1998) (FIG. 1A). Engineered NDVvectors expressing the full length human codon optimized SARS CoV-2spike protein (NDV-FLS), spike protein with 19 amino acids deleted fromits C-terminus (NDV-Δ19S), which has been shown to promote moreefficient incorporation of spike protein into lentiviral (Johnson, M.C., et al 2020) and VSV (Fukushi, S., et al 2005) particles, and GFP(NDV-GFP), between the P and M genes (FIG. 1A). Recombinant viruses wereinitially verified by immunofluorescence analysis of ribonucleoprotein(RNP) complex expression in NDV-FLS, NDV-119S and NDV-GFP infected DF-1cells (FIG. 1B) and by RT-PCR confirmation of spike gene insertion (FIG.1C). Western blot analysis of whole cell lysates from DF-1 cellsinfected with NDV-FLS or NDV-Δ19S showed robust expression of the fulllength spike protein, and in the case of NDV-FLS infected cells, weakexpression of the cleaved S1 receptor-binding subunit (FIG. 1D). Toinvestigate whether the spike protein expressed from NDV would beincorporated into the NDV virion, virus purified by gradientultracentrifugation was subjected to Western blot analysis. As shown inFIG. 1E, spike protein was incorporated into the virion of the NDV-FLSvirus; however, spike protein lacking 19 amino acids from C-terminus waspoorly incorporated into the NDV virion, and was only visible afterover-exposure of the Western blot (FIG. 2 ). Next, the spike protein wasincorporated into the NDV virion to determine whether it would increaseNDV infectivity in HEK 293T cells over-expressing humanangiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2.Using a 119S pseudotyped lentivirus neutralization assay, it was shownthat neutralizing antibodies against SARS-CoV-2 spike do not affectNDV-FLS or NDV-Δ19S infection (FIG. 3 ) indicating that incorporation ofspike protein on the surface of the NDV virion does not alterinfectivity or tropism of the vaccine.

To investigate whether expressing the SARS-CoV-2 spike protein, whichretains its multi-basic cleavage site, would impact the fusogenicproperties of NDV, DF-1 cells were infected with NDV-FLS, NDV-Δ19S orNDV-GFP and the number of multinucleated syncytia quantified. As shownin FIG. 1F, all three viruses formed syncytia in the presence oftrypsin. This shows that NDV expressing the spike protein is not morefusogenic than the parental NDV-GFP, suggesting that the spike protein,which has a multi-basic cleavage site, is not enhancing the fusogenicityof the NDV-FLS vaccine. However, NDV-expressing the FLS formedsignificantly smaller sized syncytia compared to either NDV-Δ19S orNDV-GFP (FIG. 1G).

Finally, to confirm that engineering NDV to express FLS, Δ19S or GFPdoes not alter pathogenicity of NDV in its host species, mean death time(MDT) in embryonated chicken eggs was determined. All viruses had anMDT>110 hours and thus retained their lentogenic phenotype.

Taken together, these data demonstrate that NDV can be engineered toexpress the SARS-CoV-2 spike protein without altering the safety profileof this viral vector. Moreover, the full length spike protein isincorporated into the NDV virion more efficiently than the Δ19 truncatedversion. Inventors have herein provided engineered synthetic molecularclones that are advantageous over other molecular clones of NDV in that,for example, unique restriction sites introduced allow for efficientinsertion of transgenes between the P and M genes in an orientationdependent manner as well as allow for the exchange of the F and HNgenes, for example, with those from other paramyxoviruses.

Example 1B: Engineered Chimeric NDV Vector

Inventors have also engineered and rescued a chimeric NDV virus that hasthe F protein and HN protein from avian paramyxovirus 5 (APMV5) (SEQ IDNO. 4). F protein and HN protein are constituents of the NDV envelope,embedded within the lipid bilayer membrane. The inventors designed andproduced this chimeric virus because the APMV5 F gene also has amulti-basic cleavage site, which, without wishing to be bound by theory,can be useful for fusion with cells. Since APMV-5 is not pathogenic inchickens the swapping of portion of NDV F protein with APMV5 F proteinwould broaden the use of this virus as an oncolytic agent injurisdictions where there are restrictions imposed on avian pathogens,for example in the US by the authority of USDA/CDC. Specifically, forthe NDV-APMV5 F-HN chimeric molecular clone sequence, NDV-APMV5 F iscomposed mostly of APMV5 but the last 53 amino acid are from NDV.NDV-APMV5 HN is composed mostly of APMV5 but the first 53 amino acidsare from NDV.

Example 1C: Screening Tool and Method for Selecting Stable EngineeredNDV Clones

Inventors have also developed a visual screening tool for selectingpositive, stable engineered clones based on their growth pattern onLuria-Bertani (LB) plates. Normally, molecular clone of NDV is unstablein most strains of E coli (e.g. Stellar, DH5alpha, GT116) in so for alarge portion of the polymerase gene (L) would be deleted resulting inthe growth of large and small colonies. The large colonies invariablypossessed deletions in the L gene. However, inventors showed thatselection of small colonies (about 0.5 mm to about 1 mm in diameterafter 24 h of growth) followed by multiple rounds of growth in LB brothfollowed by selection of small colonies on LB-Kanamycin plates resultedin selection of bacteria that formed small colonies and harbored stablemolecular clones of NDV.

Example 2: Lyophilized NDV-FLS Retains its Infectivity Materials andMethods

Triplicate samples of freshly harvested allantoic fluid containingNDV-FLS were aliquoted into 15 mL conical tubes in 1 mL volumes.Aliquots were either left untreated or adjusted to a final concentrationof 5% sucrose, 5% sucrose/5% Iodixanol or mixed 1:1 with a solutioncontaining 10% Lactose, 2% peptone, 10 mM Tris-HCl, pH 7.6. Using aLABCONCO Freeze Dry system Freezone®4.5, samples were immediatelylyophilized at 44×10-3 MBAR and −52° C. for 16 hours. Lyophilizedsamples were stored at 4° C. for 48 hours before being resuspended in 1mL 5% sucrose/PBS and titered. Three 1 mL aliquots of allantoic fluidcontaining NDV-FLS were adjusted to 5% sucrose and frozen at −80° C.before titering. An additional three 1 mL aliquots were used to titerNDV-FLS in allantoic fluid immediately following harvest from eggs. Allsamples were titered by TCID50 on DF-1 cells as described above.

Results

Inventors demonstrated that NDV-FLS can be lyophilized to simplifystorage and distribution requirements, without significant negativeeffects. Aliquots of NDV-FLS were brought to a final concentration of 5%sucrose, 5% sucrose/5% Iodixanol or mixed 1:1 with a solution containing10% lactose, 2% peptone, 10 mM Tris-HCl, pH 7.6 and lyophilized for 16 hat −52° C. Two days later, samples were reconstituted and virus titerdetermined as shown in FIG. 4 . There was a ˜2-fold loss of infectivitywhen NDV-FLS is lyophilized in 10% lactose, 2% peptone, 10 mM Tris-HCl,pH 7.6 compared to virus frozen at −70° C.; however, given theconvenience and greatly simplified storage and transportationrequirements of a lyophilized vaccine, this reduction in infectivity isan acceptable tradeoff.

Example 3: Engineered NDV Vector as a Vaccine for COVID-19 in MiceMethods and Materials T Cell Responses

Male Balb/c mice were administered intranasally various doses of avaccine comprising NDV that expresses the spike protein from SARS-CoV-2(NDV-FLS). After 32 days, mice were boosted with the same dose ofvaccine via the same route of administration. Five days after boost, themice were euthanized and spike protein-specific CD8+ T cell and CD4+ Tcell responses were quantified in the blood, spleen, bronchoalveolarfluid, and lung.

Intranasal Vs Intramuscular Administration

Male C57BL/6 or Balb/c mice were vaccinated either intranasally orintramuscularly with 5×10⁶ PFU NDV-FLS. At day 10 post-vaccineadministration, a subset (n=4) of mice were terminally bled and thespike protein specific CD8+ and CD4+ T cell responses quantified. Micewere non-terminally bled prior to being boosted on day 28 with the samedose of vaccine, and then bled again on days 5 and 10 post-boost, andspike protein specific CD8+ and CD4+ T cell responses quantified. Inaddition, at 10 days post-boost, bronchoalveolar lavage fluid wascollected and measured for SARS-CoV-2 spike protein-specific IgAantibodies.

Results

Inventors show that administration of engineered NDV vector expressingSARS-CoV-2 spike protein to mice elicits humoral and cellular responses.SARS-CoV-2 spike protein-specific CD8+ T cell and CD4+ T cell responseswere detected quantified and are shown in FIG. 5 and FIG. 6 ,respectively. SARS-CoV-2 spike protein specific CD8+ and CD4+ T cellresponses after intranasal or intramuscular administration weredetected, quantified and compared, as shown in FIG. 7 . As well, robustanti-spike IgA antibodies were detected in the Balb/c strain of miceafter intranasal delivery of the NDV-FLS spike using a primer (5×10⁶PFU) boost (5×10⁶ PFU) regimen (see Table 2).

TABLE 2 Spike-specific IgA antibodies in bronchoalveolar lavage fluidIgA Treatment Dilution OD1 Dilution OD1 Dilution OD1 Dilution OD1Dilution OD1 Dilution OD1 NDV-FLS I.N C57BL6 1:5 0.063 0 NDV-FLS I.NC57BL6 1:5 0.113 0 NDV-FLS I.N C57BL6 1:5 0.101 0 NDV-FLS I.N C57BL6 1:50.125 1:10 0.045 NDV-FLS I.N BalbC 1:5 0.124 1:10 0.074 1:20 0.041NDV-FLS I.N BalbC 1:5 0.51 1:10 0.173 1:20 0.206 1:40 0.015 NDV-FLS I.NBalbC 1:5 0.236 1:10 0.142 1:20 0.09 1:40 0.075 1:80 0.083 1:160 0.036NDV-FLS I.N BalbC 1:5 0.012 1:10 0 1:20 0.712 NDV-FLS I.M C57BL6 1:50.064 0 NDV-FLS I.M C57BL6 1:5 0.134 1:10 0.028 1:20 0.006 1:40 0.344NDV-FLS I.M C57BL6 1:5 0 0 NDV-FLS I.M C57BL6 1:5 0.047 0 NDV-FLS I.MBalbC 1:5 0 0 NDV-FLS I.M BalbC 1:5 0 0 NDV-FLS I.M BalbC 1:5 0 0

Thus, inventors have demonstrated that the engineered NDV vectormolecular clone designed to express the SARS-CoV-2 spike protein(NDV-FLS) leads to the production of spike protein-specific serum IgGand mucosal IgA antibodies as well as spike protein-specific T cellsresponses in mice administered with the NDV-FLS vaccine intranasally.

Example 4: Engineered NDV Vector Kills Tumor Cells In Vitro

The ability of engineered NDV vector of this disclosure in killing tumorcells was tested in vitro using cells from murine acute myeloid leukemia(AML) C1498 cell line. Cultured C1498 cells were treated with NDV-GFP-NY(Park M-S et al, PNAS 2006; Gao Q et al, J Virol 2008), mesogenicNDV-GFP-GM (which has a 3 amino acid change in the F gene that makes itmesogenic (i.e. fusogenic), i.e. from GRQGRL to RRQRRF at amino acidpositions 112, 115, and 117 in reference SEQ ID NO: 28, or lentogenicNDV-GFP-GL at varying MOI, and metabolic activity relative to untreatedcells were measured by resazurin (cell proliferation) assay (FIG. 8 ,left panel). The area under the curve in FIG. 8 , left panel was plottedin the graph on the right panel. These results show that mesogenicNDV-GFP-GM was significantly better than NDV-GFP-NY and lentogenicNDV-GFP-GL at killing C1498 cells in vitro.

Example 5: Engineered NDV Vector Stimulates NK Cells in Ovarian TumorBearing Mice

The ability of engineered NDV vector to stimulate the immune system wastested in a model of ovarian tumor bearing mice (Russell et al., 2015).These tumor bearing mice were injected with phosphate-buffered salinemock control, adeno-associated virus (AAV) expressing thrombospondin-1type I repeats (3TSR), AAV expressing Fc3TSR, or AAV expressingbevacizumab, in the absence or presence of engineered NDV-GFP-GM vector.The 3TSR is a glycoprotein with potent anti-angiogenic factor, which isused in cancer treatment; Fc3TSR is a stabilized form of thisglycoprotein. Bevacizumab is a recombinant antibody targeting thevascular endothelial growth factor (VEGF), a pro-angiogenic protein. Inthis Example, 3TSR, Fc3TSR and bevazicumab were expressed by anadeno-associated virus, and used in combination with NDV-GFP deliveredintravenously. Blood was obtained from the mice via retro-orbital bleeds36 hours post NDV-GFP infection. Red blood cells were lysed, andremaining cells were stained via flow cytometry to analyze for markersindicative of immune stimulation. Over 90% NK cells were detected toexpress the early activation marker CD69 (FIG. 9A) and over 20% NK cellswere PD-L1+ in all groups injected with the engineered NDV-GFP vector,but there was negligible detection in its absence. Granzyme B+ andIFNy+NK cells were also detected in the engineered NDV-GFP vector groupbut not in its absence (FIG. 9B). Together, these results demonstratedthat NDV-GFP leads to the potent stimulation of NK cells in ovariantumor bearing mice. NDV of the present disclosure is useful as anoncolytic agent.

Example 6: NDV-Prefusion Stabilized SARS-CoV-2 Spike (NDV-PFS) ProtectsAgainst SARS-CoV-2 in Hamsters Prefusion Stabilized SARS-CoV-2 Spike(PFS) Expression

Expression of prefusion stabilized SARS-CoV-2 spike (PFS; SEQ ID NO: 41)in the allantoic fluid of embryonated eggs inoculated with NDV-PFS (SEQID NO: 4) was determined by Western immunoblotting. A 6% SDS-PAGE geland rabbit anti-SARS-CoV-2 S1 (dilution: 1:1000; PA5-81795;ThermoFisher) was used for detection of SARS-CoV-2 spike (FIG. 10 ;black arrow). A 10% SDS-PAGE gel and mouse anti-NDV ribonucleoprotein(dilution: 1:5000; NBP2-11633; Novus Biologicals) was used for detectionof NDV. 20 μL of allantoic fluid was loaded in for samples. NDV-GFP wasloaded as a control. MW used was the PageRuler™ Plus Prestained ProteinLadder (Thermo Scientific). These results showed robust expression ofSARS-CoV-2 S1 from embryonated eggs inoculated with NDV-PFS, indicatingthe ability of this NDV platform for delivering a payload such asSARS-CoV-2 S1.

Protection from Weight Loss in NDV-COVID-19 Vaccinated HamstersChallenged with SARS-CoV-2

The inventors next determined the effects of NDV-PFS vaccination onhamsters challenged with SARS-CoV-2. Groups of eight Syrian Goldenhamsters (four male and four female, four to six weeks of age; CharlesRiver) were anaesthetized with inhalation isoflurane and administered1E7 PFU/animal of recombinant NDV-GFP, NDV-FLS, or NDV-PFS via theintranasal (IN) route. For IN vaccinations, anaesthetized hamsters werescruffed and vaccines were delivered in a 100 μL volume (q.s. with PBS)through the nares (50 μL per nare). Animals had their mouths held closedto ensure inhalation through the nose. For the prime/boost groups, 28days following the initial vaccine administration, hamsters wereadministered a second dose of the homologous vaccine (1E7 PFU/animal byIN route). At 28 days post-prime or 28 days post-prime/boost, hamsterswere moved into a CL-3 facility, anaesthetized with inhaled isofluraneand infected SARS-CoV-2 via the same IN method described above.Challenge dose: Alpha variant @ 8.5E4 PFU/animal by IN, Ancestral(Wuhan) @ 1E5 PFU/animal by IN. After recovery from anesthetic hamsterswere monitored daily throughout the course of infection. FIG. 11 showsgraphs of results of body weights of hamsters, which were recorded daily(error bars represent mean+/−SEM). These results showed thatNDV-COVID-19 vaccination, in particular NDV-PFS vaccination, providedprotection from weight loss in hamsters challenged with SARS-CoV-2,whether with the alpha variant or the ancestral strain.

Reduced SARS-CoV-2 Viral RNA Copies in the Lung and Nasal Turbinates ofVaccinated and Challenged Syrian Hamsters

The effects of NDV-COVID-19 vaccination on SARS-CoV-2 viral RNA copiesin the lung and nasal turbinates in hamsters were determined. Thehamsters were vaccinated and challenged as above, and at 5 days postchallenge with Alpha variant @ 8.5E4 PFU/animal by IN or Ancestral(Wuhan) @ 1E5 PFU/animal by IN, vaccinated hamsters were euthanized andviral RNA copies in the lung and nasal turbinates quantified by qRT-PCR.RNA was extracted with the QIAamp Viral RNA Mini kit (Qiagen) andreverse transcribed and amplified using the primers reported by the WHOand include E_Sarbeco_F1 (5′-ACAGGTACGTTAATAGTTAATAGCGT-3′; SEQ ID NO:37) and E_Sarbeco_R2 (5′-ATATTGCAGCAGTA CGCACACA-3′; SEQ ID NO: 38) andprobe E_Sarbeco_P1 (5′-FAM-ACACTAGCCATCCTTACTGCGCTTCG-BBQ-3′; SEQ ID NO:39). A standard curve produced with synthesized target DNA was run withevery plate and used for the interpolation of viral genome copy numbers.FIG. 12 shows graphs of viral RNA levels reported as genome copy number(error bars represent mean+/−SEM). Differences in the magnitude of viruscopy number were assessed by Kruskall-Wallis test with Dunn's test formultiple comparisons. These results showed that NDV-COVID-19vaccination, in particular NDV-PFS vaccination, reduced SARS-CoV-2 viralRNA copies in the lung and nasal turbinates of hamsters challenged withSARS-CoV-2, whether with the alpha variant or the ancestral strain.

Reduced Infectious SARS-CoV-2 in the Lung and Nasal Turbinates ofVaccinated and Challenged Syrian Hamsters

The effects of NDV-COVID-19 vaccination on infectious SARS-CoV-2 in thelung and nasal turbinates in hamsters were determined. The hamsters werevaccinated and challenged as above, and at 5 days post challenge withAlpha variant @ 8.5E4 PFU/animal by IN or Ancestral (Wuhan) @ 1E5PFU/animal by IN, vaccinated hamsters were euthanized and infectioustiters of SARS-CoV-2 in the lung and nasal turbinates determined. Forinfectious virus assays, thawed tissue samples were weighed and placedin 1 mL of minimum essential medium supplemented with 1%heat-inactivated fetal bovine serum (FBS) and 1×L-glutamine, thenhomogenized in a Bead Ruptor Elite Bead Mill Homogenizer (OmniInternational) at 4 m/s for 30 seconds then clarified by centrifugationat 1,500×g for 10 minutes. Samples were serially diluted 10-fold inmedia and dilutions were then added to 96-well plates of 95% confluentVero cells containing 50 μL of the same medium in replicates of threeand incubated for five days at 37° C. with 5% CO₂. FIG. 13 shows graphsof results from plates that were scored for the presence of cytopathiceffect on day five after infection, and the titers were calculated usingthe Reed-Muench method, converted to PFU after multiplying by 0.69 andreported as PFU/g of tissue. These results showed that NDV-COVID-19vaccination, in particular NDV-PFS vaccination, reduced infectiousSARS-CoV-2 in the lung and nasal turbinates of hamsters challenged withSARS-CoV-2, whether with the alpha variant or the ancestral strain.Together, these results showed that NDV-COVID-19 of the presentdisclosure, including NDV-PFS, is a useful platform for vaccine againstCOVID-19.

While the present disclosure has been described with reference to whatare presently considered to be the preferred example, it is to beunderstood that the disclosure is not limited to the disclosed example.To the contrary, the disclosure is intended to cover variousmodifications and equivalent arrangements included within the spirit andscope of the appended claims.

All publications, patents and patent applications are hereinincorporated by reference in their entirety to the same extent as ifeach individual publication, patent or patent application wasspecifically and individually indicated to be incorporated by referencein its entirety.

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1. An engineered Newcastle Disease Virus (NDV) vector comprising anucleic acid having a nucleic acid sequence that is at least 95% or 100%identical to the nucleic acid sequence of any one of SEQ ID NO: 1-5, 9,10, 18, 19, 23, 27, or 42, wherein the nucleic acid comprises or furthercomprises at least one heterologous nucleic acid segment encoding atherapeutic agent operably linked to a promoter capable of expressingthe segment in a host cell, wherein the nucleic acid comprises a nucleicacid sequence encoding an L protein having a stabilizing segment, andwherein the nucleic acid comprises XbaI and MluI restrictionendonuclease sites between nucleic acid sequence encoding phosphoproteinand matrix protein.
 2. The engineered NDV vector claim 1, comprising anucleic acid having a nucleic acid sequence that is at least 95% or 100%identical to the nucleic acid sequence of SEQ ID NO: 9, 10, 23, or 27.3. The engineered NDV vector of claim 1, wherein the therapeutic agentcomprises a SARS-CoV-2 spike protein.
 4. The engineered NDV vector ofclaim 3, wherein the SARS-CoV-2 spike protein comprises an amino acidsequence having at least 95% identity to the amino acid sequence of SEQID NO: 6, 7, 29, 30, 31, or
 41. 5. The engineered NDV vector of claim 1,comprising a nucleic acid having a nucleic acid sequence a chimeric Fprotein, and a chimeric HN protein, wherein the chimeric F proteincomprises avian paramyxovirus 5 (APMV5) F protein segment thereof at theN-terminus and an NDV F protein segment at the C-terminus, and whereinthe chimeric HN protein comprises an NDV HN protein segment at theN-terminus and an AMPV5 HN protein segment at the C-terminus.
 6. Anengineered Newcastle Disease Virus (NDV) vector comprising a nucleicacid having a nucleic acid sequence encoding an L protein having astabilizing segment, a chimeric F protein, and a chimeric HN protein,wherein the chimeric F protein comprises avian paramyxovirus 5 (APMV5) Fprotein segment thereof at the N-terminus and an NDV F protein segmentat the C-terminus, and wherein the chimeric HN protein comprises an NDVHN protein segment at the N-terminus and an AMPV5 HN protein segment atthe C-terminus.
 7. The engineered NDV vector of claim 6, wherein thenucleic acid comprises XbaI and MluI restriction endonuclease sitesbetween nucleic acid sequence encoding phosphoprotein and matrixprotein.
 8. The engineered NDV vector of claim 6, wherein thestabilizing segment comprises an amino acid sequence as set forth in SEQID NO: 20, or comprises an amino acid sequence encoded by a nucleic acidcomprising a nucleic acid sequence as set forth in SEQ ID NO:
 35. 9. Theengineered NDV vector of claim 6, wherein the chimeric F proteincomprises at the C-terminus 53 amino acid of NDV F protein from aminoacid positions 501 to 553 of SEQ ID NO: 28, or the chimeric HN proteincomprises at the N-terminus 53 amino acids of NDV HN protein from aminoacid positions 1 to 53 of SEQ ID NO:
 34. 10. The engineered NDV vectorof claim 6, wherein the L protein comprises an amino acid sequencehaving at least 95% identity to the amino acid sequence as set forth inSEQ ID NO: 11, the chimeric F protein comprises an amino acid sequencehaving at least 95% identity to the amino acid sequence of SEQ ID NO:12, and/or the chimeric HN protein comprises an amino acid sequencehaving at least 95% identity to the amino acid sequence of SEQ ID NO:13.
 11. The engineered NDV vector of claim 6, wherein the NDV vector islentogenic, and wherein the nucleic acid comprises a nucleic acidsequence of SEQ ID NO:
 25. 12. The engineered NDV vector of claim 6,wherein the nucleic acid further comprises at least one heterologousnucleic acid segment encoding a therapeutic agent operably linked to apromoter capable of expressing the segment in a host cell.
 13. Theengineered NDV vector of claim 6, wherein the therapeutic agentcomprises a SARS-CoV-2 spike protein.
 14. The engineered NDV vector ofclaim 13, wherein the SARS-CoV-2 spike protein comprises an amino acidsequence having at least 95% identity to the amino acid sequence of SEQID NO: 6, 7, 29, 30, 31, or
 41. 15. An immunogenic composition,oncolytic agent, or vaccine comprising the engineered NDV vector ofclaim
 6. 16. A method for treating a disease, comprising administeringto a subject the engineered NDV vector of claim
 6. 17. A method ofeliciting an immune response, comprising administering to a subject theengineered NDV vector of claim
 6. 18. A method of treating cancer,comprising administering to a subject the engineered NDV vector of claim1, wherein the NDV vector comprises a nucleic acid having a nucleic acidsequence that is at least 95% or 100% identical to the nucleic acidsequence of any one of SEQ ID NO: 1, 5, 9, 10, 23, or
 27. 19. A methodfor selecting an engineered NDV vector genome comprising a stabilizingsegment in L gene, the method comprises: a) growing bacterial cellscomprising an engineered NDV vector genome in a growth medium broth; b)growing the bacterial cells on an agar-growth medium, wherein theagar-growth medium comprises a selection agent; c) identifying smallbacterial cell colonies having about 0.5 mm to about 1 mm in diameterafter at least 24 hours of growth; d) repeating step a) to step c) twoto nine times to enrich for small bacterial cell colonies; and e)isolating the engineered NDV vector genome from the small bacterialcells colonies, wherein the small bacterial cells colonies comprisestable engineered NDV vector genome having the stabilizing segment in Lgene.